Displaying publications 81 - 100 of 109 in total

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  1. Munirah S, Kim SH, Ruszymah BH, Khang G
    Eur Cell Mater, 2008 Feb 21;15:41-52.
    PMID: 18288632
    Our preliminary results indicated that fibrin and poly(lactic-co-glycolic acid) (PLGA) hybrid scaffold promoted early chondrogenesis of articular cartilage constructs in vitro. The aim of this study was to evaluate in vivo cartilaginous tissue formation by chondrocyte-seeded fibrin/PLGA hybrid scaffolds. PLGA scaffolds were soaked carefully, in chondrocyte-fibrin suspension, and polymerized by dropping thrombin-calcium chloride (CaCl2) solution. PLGA-seeded chondrocytes were used as a control. Resulting constructs were implanted subcutaneously, at the dorsum of nude mice, for 4 weeks. Macroscopic observation, histological evaluation, gene expression and sulphated-glycosaminoglycan (sGAG) analyses were performed at each time point of 1, 2 and 4 weeks post-implantation. Cartilaginous tissue formation in fibrin/PLGA hybrid construct was confirmed by the presence of lacunae and cartilage-isolated cells embedded within basophilic ground substance. Presence of proteoglycan and glycosaminoglycan (GAG) in fibrin/PLGA hybrid constructs was confirmed by positive Safranin O and Alcian Blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrices. Chondrogenic properties were further demonstrated by the expression of gene encoded cartilage-specific markers, collagen type II and aggrecan core protein. The sGAG production in fibrin/PLGA hybrid constructs was higher than in the PLGA group. In conclusion, fibrin/PLGA hybrid scaffold promotes cartilaginous tissue formation in vivo and may serve as a potential cell delivery vehicle and a structural basis for articular cartilage tissue-engineering.
    Matched MeSH terms: Extracellular Matrix/metabolism
  2. Baie SH, Sheikh KA
    J Ethnopharmacol, 2000 Nov;73(1-2):15-30.
    PMID: 11025135
    Haruan has been proved to influence the different phases of wound healing process. The current research focuses on the effects of haruan on the different constituents of extracellular matrix of healing wounds in normal and diabetic rats. Anaesthetized normal and streptozotocin induced diabetic rats were provided with excision wounds at the back and then animals were divided into four groups as: group 1, wounds treated with cetrimide+haruan cream; group 2, wounds treated with haruan cream; group 3, wounds treated with cetrimide (commercial) cream; and group 4, wounds untreated and served as control. Animals were sacrificed after 3, 6, 9 and 12 days. These wounds were used to determine the hexosamine, protein, uronic acid and glycosaminoglycan contents and the wound contraction. The results suggested a marked increase (P<0.05) in the uronic acid, hexosamine and dermatan sulfate contents on day 3 of group 1 when compared with groups 2-4. Wound contraction of group 1 was also markedly enhanced of group 1 (P<0.01) when compared with groups 2- 4. On the basis of these results, we conclude that haruan enhances the synthesis of different glycosaminoglycans in healing wounds, which are the first component of extracellular matrix to be synthesized during the wound healing process. The enhanced levels of glycosaminoglycans may help in the formation of a resistant scar and enhanced wound contraction represents the positive influence of haruan on the fibroplastic phase of wound healing.
    Matched MeSH terms: Extracellular Matrix/metabolism*
  3. Nam HY, Balaji Raghavendran HR, Pingguan-Murphy B, Abbas AA, Merican AM, Kamarul T
    PLoS One, 2017;12(6):e0178117.
    PMID: 28654695 DOI: 10.1371/journal.pone.0178117
    The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated. In order to establish this, we disrupted calcium signalling by blocking stretch-activated calcium channel (SACC) in human MSCs (hMSCs) in vitro. Passaged-2 hMSCs were exposed to cyclic tensile loading (1 Hz + 8% for 6, 24, 48, and 72 hours) in the presence of the SACC blocker, gadolinium. Analyses include image observations of immunochemistry and immunofluorescence staining from extracellular matrix (ECM) production, and measuring related tenogenic and apoptosis gene marker expression. Uniaxial tensile loading increased the expression of tenogenic markers and ECM production. However, exposure to strain in the presence of 20 μM gadolinium reduced the induction of almost all tenogenic markers and ECM staining, suggesting that SACC acts as a mechanosensor in strain-induced hMSC tenogenic differentiation process. Although cell death was observed in prolonged stretching, it did not appear to be apoptosis mediated. In conclusion, the knowledge gained in this study by elucidating the role of calcium in MSC mechanotransduction processes, and that in prolonged stretching results in non-apoptosis mediated cell death may be potential useful for regenerative medicine applications.
    Matched MeSH terms: Extracellular Matrix/metabolism
  4. Samuel S, Ahmad RE, Ramasamy TS, Karunanithi P, Naveen SV, Kamarul T
    Platelets, 2019;30(1):66-74.
    PMID: 29090639 DOI: 10.1080/09537104.2017.1371287
    Platelet-rich concentrate (PRC), used in conjunction with other chondroinductive growth factors, have been shown to induce chondrogenesis of human mesenchymal stromal cells (hMSC) in pellet culture. However, pellet culture systems promote cell hypertrophy and the presence of other chondroinductive growth factors in the culture media used in previous studies obscures accurate determination of the effect of platelet itself in inducing chondrogenic differentiation. Hence, this study aimed to investigate the effect of PRC alone in enhancing the chondrogenic differentiation potential of human mesenchymal stromal cells (hMSC) encapsulated in three-dimensional alginate constructs. Cells encapsulated in alginate were cultured in serum-free medium supplemented with only 15% PRC. Scanning electron microscopy was used to determine the cell morphology. Chondrogenic molecular signature of hMSCs was determined by quantitative real-time PCR and verified at protein levels via immunohistochemistry and enzyme-linked immunosorbent assay. Results showed that the cells cultured in the presence of PRC for 24 days maintained a chondrocytic phenotype and demonstrated minimal upregulation of cartilaginous extracellular matrix (ECM) marker genes (SOX9, TNC, COL2, ACAN, COMP) and reduced expression of chondrocyte hypertrophy genes (Col X, Runx2) compared to the standard chondrogenic medium (p 
    Matched MeSH terms: Extracellular Matrix/metabolism*
  5. Leon AJ, Borisevich V, Boroumand N, Seymour R, Nusbaum R, Escaffre O, et al.
    PLoS Negl Trop Dis, 2018 03;12(3):e0006343.
    PMID: 29538374 DOI: 10.1371/journal.pntd.0006343
    Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.
    Matched MeSH terms: Extracellular Matrix/genetics
  6. Rayagiri SS, Ranaldi D, Raven A, Mohamad Azhar NIF, Lefebvre O, Zammit PS, et al.
    Nat Commun, 2018 03 14;9(1):1075.
    PMID: 29540680 DOI: 10.1038/s41467-018-03425-3
    A central question in stem cell biology is the relationship between stem cells and their niche. Although previous reports have uncovered how signaling molecules released by niche cells support stem cell function, the role of the extra-cellular matrix (ECM) within the niche is unclear. Here, we show that upon activation, skeletal muscle stem cells (satellite cells) induce local remodeling of the ECM and the deposition of laminin-α1 and laminin-α5 into the basal lamina of the satellite cell niche. Genetic ablation of laminin-α1, disruption of integrin-α6 signaling or blocking matrix metalloproteinase activity impairs satellite cell expansion and self-renewal. Collectively, our findings establish that remodeling of the ECM is an integral process of stem cell activity to support propagation and self-renewal, and may explain the effect laminin-α1-containing supports have on embryonic and adult stem cells, as well as the regenerative activity of exogenous laminin-111 therapy.
    Matched MeSH terms: Extracellular Matrix/metabolism
  7. Agarwal R, Agarwal P
    Exp Biol Med (Maywood), 2017 Feb;242(4):374-383.
    PMID: 27798117 DOI: 10.1177/1535370216675065
    Disturbances of extracellular matrix homeostasis are associated with a number of pathological conditions. The ability of extracellular matrix to provide contextual information and hence control the individual or collective cellular behavior is increasingly being recognized. Hence, newer therapeutic approaches targeting extracellular matrix remodeling are widely investigated. We reviewed the current literature showing the effects of resveratrol on various aspects of extracellular matrix remodeling. This review presents a summary of the effects of resveratrol on extracellular matrix deposition and breakdown. Mechanisms of action of resveratrol in extracellular matrix deposition involving growth factors and their signaling pathways are discussed. Involvement of phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways and role of transcription factors and sirtuins on the effects of resveratrol on extracellular matrix homeostasis are summarized. It is evident from the literature presented in this review that resveratrol has significant effects on both the synthesis and breakdown of extracellular matrix. The major molecular targets of the action of resveratrol are growth factors and their signaling pathways, phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways, transcription factors, and SIRT-1. The effects of resveratrol on extracellular matrix and the molecular targets appear to be related to experimental models, experimental environment as well as the doses.
    Matched MeSH terms: Extracellular Matrix/pathology*
  8. Ayele T, Zuki AB, Noorjahan BM, Noordin MM
    J Mater Sci Mater Med, 2010 May;21(5):1721-30.
    PMID: 20135201 DOI: 10.1007/s10856-010-4007-7
    The aim of this study was to engineer skeletal muscle tissue for repair abdominal wall defects. Myoblast were seeded onto the scaffolds and cultivated in vitro for 5 days. Full thickness abdominal wall defects (3 x 4 cm) were created in 18 male New Zealand white rabbits and randomly divided into two equal groups. The defects of the first group were repaired with myoblast-seeded-bovine tunica vaginalis whereas the second group repaired with non-seeded-bovine tunica vaginalis and function as a control. Three animals were sacrificed at 7th, 14th, and 30th days of post-implantation from each group and the explanted specimens were subjected to macroscopic and microscopic analysis. In every case, seeded scaffolds have better deposition of newly formed collagen with neo-vascularisation than control group. Interestingly, multinucleated myotubes and myofibers were only detected in cell-seeded group. This study demonstrated that myoblast-seeded-bovine tunica vaginalis can be used as an effective scaffold to repair severe and large abdominal wall defects with regeneration of skeletal muscle tissue.
    Matched MeSH terms: Extracellular Matrix
  9. Boyle ST, Mittal P, Kaur G, Hoffmann P, Samuel MS, Klingler-Hoffmann M
    J Proteome Res, 2020 10 02;19(10):4093-4103.
    PMID: 32870688 DOI: 10.1021/acs.jproteome.0c00511
    Tumorigenesis involves a complex interplay between genetically modified cancer cells and their adjacent normal tissue, the stroma. We used an established breast cancer mouse model to investigate this inter-relationship. Conditional activation of Rho-associated protein kinase (ROCK) in a model of mammary tumorigenesis enhances tumor growth and progression by educating the stroma and enhancing the production and remodeling of the extracellular matrix. We used peptide matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to quantify the proteomic changes occurring within tumors and their stroma in their regular spatial context. Peptides were ranked according to their ability to discriminate between the two groups, using a receiver operating characteristic tool. Peptides were identified by liquid chromatography tandem mass spectrometry, and protein expression was validated by quantitative immunofluorescence using an independent set of tumor samples. We have identified and validated four key proteins upregulated in ROCK-activated mammary tumors relative to those expressing kinase-dead ROCK, namely, collagen I, α-SMA, Rab14, and tubulin-β4. Rab14 and tubulin-β4 are expressed within tumor cells, whereas collagen I is localized within the stroma. α-SMA is predominantly localized within the stroma but is also expressed at higher levels in the epithelia of ROCK-activated tumors. High expression of COL1A, the gene encoding the pro-α 1 chain of collagen, correlates with cancer progression in two human breast cancer genomic data sets, and high expression of COL1A and ACTA2 (the gene encoding α-SMA) are associated with a low survival probability (COLIA, p = 0.00013; ACTA2, p = 0.0076) in estrogen receptor-negative breast cancer patients. To investigate whether ROCK-activated tumor cells cause stromal cancer-associated fibroblasts (CAFs) to upregulate expression of collagen I and α-SMA, we treated CAFs with medium conditioned by primary mammary tumor cells in which ROCK had been activated. This led to abundant production of both proteins in CAFs, clearly highlighting the inter-relationship between tumor cells and CAFs and identifying CAFs as the potential source of high levels of collagen 1 and α-SMA and associated enhancement of tissue stiffness. Our research emphasizes the capacity of MALDI-MSI to quantitatively assess tumor-stroma inter-relationships and to identify potential prognostic factors for cancer progression in human patients, using sophisticated mouse cancer models.
    Matched MeSH terms: Extracellular Matrix
  10. Tan CW, Ng MH, Ohnmar H, Lokanathan Y, Nur-Hidayah H, Roohi SA, et al.
    Indian J Orthop, 2013 Nov;47(6):547-52.
    PMID: 24379458 DOI: 10.4103/0019-5413.121572
    BACKGROUND AND AIM: Synthetic nerve conduits have been sought for repair of nerve defects as the autologous nerve grafts causes donor site morbidity and possess other drawbacks. Many strategies have been investigated to improve nerve regeneration through synthetic nerve guided conduits. Olfactory ensheathing cells (OECs) that share both Schwann cell and astrocytic characteristics have been shown to promote axonal regeneration after transplantation. The present study was driven by the hypothesis that tissue-engineered poly(lactic-co-glycolic acid) (PLGA) seeded with OECs would improve peripheral nerve regeneration in a long sciatic nerve defect.

    MATERIALS AND METHODS: Sciatic nerve gap of 15 mm was created in six adult female Sprague-Dawley rats and implanted with PLGA seeded with OECs. The nerve regeneration was assessed electrophysiologically at 2, 4 and 6 weeks following implantation. Histopathological examination, scanning electron microscopic (SEM) examination and immunohistochemical analysis were performed at the end of the study.

    RESULTS: Nerve conduction studies revealed a significant improvement of nerve conduction velocities whereby the mean nerve conduction velocity increases from 4.2 ΁ 0.4 m/s at week 2 to 27.3 ΁ 5.7 m/s at week 6 post-implantation (P < 0.0001). Histological analysis revealed presence of spindle-shaped cells. Immunohistochemical analysis further demonstrated the expression of S100 protein in both cell nucleus and the cytoplasm in these cells, hence confirming their Schwann-cell-like property. Under SEM, these cells were found to be actively secreting extracellular matrix.

    CONCLUSION: Tissue-engineered PLGA conduit seeded with OECs provided a permissive environment to facilitate nerve regeneration in a small animal model.

    Matched MeSH terms: Extracellular Matrix
  11. Ahn J, Lim J, Jusoh N, Lee J, Park TE, Kim Y, et al.
    PMID: 31380359 DOI: 10.3389/fbioe.2019.00168
    Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate the interactions between the TME and HA using a microfluidic platform designed for culturing tumor cells in 3D bone-mimetic composite of HA and fibrin. We developed a bone metastasis TME model from colorectal cancer (SW620) and gastric cancer (MKN74) cells, which has very poor prognosis but rarely been investigated. The microfluidic platform enabled straightforward formation of 3D TME composed the hydrogel and multiple cell types. This facilitated monitoring of the effect of HA concentration and culture time on the TME. In 3D bone mimicking culture, we found that HA rich microenvironment affects cell viability, proliferation and cancer cell cytoplasmic volume in a manner dependent on the different metastatic cancer cell types and culture duration indicating the spatial heterogeneity (different origin of metastatic cancer) and temporal heterogeneity (growth time of cancer) of TME. We also found that both SW620 and MKN72 cells exhibited significantly reduced migration at higher HA concentration in our platform indicating inhibitory effect of HA in both cancer cells migration. Next, we quantitatively analyzed angiogenic sprouts induced by paracrine factors that secreted by TME and showed paracrine signals from tumor and stromal cell with a high HA concentration resulted in the formation of fewer sprouts. Finally we reconstituted vascularized TME allowing direct interaction between angiogenic sprouts and tumor-stroma microspheroids in a bone-mimicking microenvironment composing a tunable HA/fibrin composite. Our multifarious approach could be applied to drug screening and mechanistic studies of the metastasis, growth, and progression of bone tumors.
    Matched MeSH terms: Extracellular Matrix
  12. Williams HF, Mellows BA, Mitchell R, Sfyri P, Layfield HJ, Salamah M, et al.
    PLoS Negl Trop Dis, 2019 01;13(1):e0007041.
    PMID: 30695027 DOI: 10.1371/journal.pntd.0007041
    Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage.
    Matched MeSH terms: Extracellular Matrix
  13. Loh EYX, Fauzi MB, Ng MH, Ng PY, Ng SF, Mohd Amin MCI
    Int J Biol Macromol, 2020 Sep 15;159:497-509.
    PMID: 32387606 DOI: 10.1016/j.ijbiomac.2020.05.011
    In skin tissue engineering, a biodegradable scaffold is usually used where cells grow, produce its own cytokines, growth factors, and extracellular matrix, until the regenerated tissue gradually replaces the scaffold upon its degradation. However, the role of non-biodegradable scaffold remains unexplored. This study investigates the potential of a non-biodegradable bacterial nanocellulose/acrylic acid (BNC/AA) hydrogel to transfer human dermal fibroblasts (HDF) to the wound and the resulting healing effects of transferred HDF in athymic mice. Results demonstrated that the fabricated hydrogel successfully transferred >50% of HDF onto the wound site within 24 h, with evidence of HDF detected on day 7. The gene and protein study unveiled faster wound healing in the hydrogel with HDF group and characterized more mature newly formed skin microstructure on day 7, despite no visible differences. These findings give a new perspective regarding the role of non-biodegradable materials in skin tissue engineering, in the presence of exogenous cells, mainly at the molecular level.
    Matched MeSH terms: Extracellular Matrix
  14. Rashidbenam Z, Jasman MH, Tan GH, Goh EH, Fam XI, Ho CCK, et al.
    Int J Mol Sci, 2021 Mar 25;22(7).
    PMID: 33805910 DOI: 10.3390/ijms22073350
    Long urethral strictures are often treated with autologous genital skin and buccal mucosa grafts; however, risk of hair ingrowth and donor site morbidity, restrict their application. To overcome this, we introduced a tissue-engineered human urethra comprising adipose-derived stem cell (ASC)-based self-assembled scaffold, human urothelial cells (UCs) and smooth muscle cells (SMCs). ASCs were cultured with ascorbic acid to stimulate extracellular matrix (ECM) production. The scaffold (ECM) was stained with collagen type-I antibody and the thickness was measured under a confocal microscope. Results showed that the thickest scaffold (28.06 ± 0.59 μm) was achieved with 3 × 104 cells/cm2 seeding density, 100 μg/mL ascorbic acid concentration under hypoxic and dynamic culture condition. The biocompatibility assessment showed that UCs and SMCs seeded on the scaffold could proliferate and maintain the expression of their markers (CK7, CK20, UPIa, and UPII) and (α-SMA, MHC and Smootheline), respectively, after 14 days of in vitro culture. ECM gene expression analysis showed that the ASC and dermal fibroblast-based scaffolds (control) were comparable. The ASC-based scaffold can be handled and removed from the plate. This suggests that multiple layers of scaffold can be stacked to form the urothelium (seeded with UCs), submucosal layer (ASCs only), and smooth muscle layer (seeded with SMCs) and has the potential to be developed into a fully functional human urethra for urethral reconstructive surgeries.
    Matched MeSH terms: Extracellular Matrix
  15. Lo S, Fauzi MB
    Pharmaceutics, 2021 Feb 28;13(3).
    PMID: 33670973 DOI: 10.3390/pharmaceutics13030316
    Tissue engineering technology is a promising alternative approach for improvement in health management. Biomaterials play a major role, acting as a provisional bioscaffold for tissue repair and regeneration. Collagen a widely studied natural component largely present in the extracellular matrix (ECM) of the human body. It provides mechanical stability with suitable elasticity and strength to various tissues, including skin, bone, tendon, cornea and others. Even though exogenous collagen is commonly used in bioscaffolds, largely in the medical and pharmaceutical fields, nano collagen is a relatively new material involved in nanotechnology with a plethora of unexplored potential. Nano collagen is a form of collagen reduced to a nanoparticulate size, which has its advantages over the common three-dimensional (3D) collagen design, primarily due to its nano-size contributing to a higher surface area-to-volume ratio, aiding in withstanding large loads with minimal tension. It can be produced through different approaches including the electrospinning technique to produce nano collagen fibres resembling natural ECM. Nano collagen can be applied in various medical fields involving bioscaffold insertion or fillers for wound healing improvement; skin, bone, vascular grafting, nerve tissue and articular cartilage regeneration as well as aiding in drug delivery and incorporation for cosmetic purposes.
    Matched MeSH terms: Extracellular Matrix
  16. Papadaki V, Asada K, Watson JK, Tamura T, Leung A, Hopkins J, et al.
    Cancers (Basel), 2020 Nov 13;12(11).
    PMID: 33202923 DOI: 10.3390/cancers12113362
    Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-β and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer.
    Matched MeSH terms: Extracellular Matrix Proteins
  17. Imran SAM, Yazid MD, Idrus RBH, Maarof M, Nordin A, Razali RA, et al.
    Int J Mol Sci, 2021 Apr 09;22(8).
    PMID: 33918710 DOI: 10.3390/ijms22083888
    Epithelial-Mesenchymal Transition (EMT) was first discovered during the transition of cells from the primitive streak during embryogenesis in chicks. It was later discovered that EMT holds greater potential in areas other than the early development of cells and tissues since it also plays a vital role in wound healing and cancer development. EMT can be classified into three types based on physiological functions. EMT type 3, which involves neoplastic development and metastasis, has been the most thoroughly explored. As EMT is often found in cancer stem cells, most research has focused on its association with other factors involving cancer progression, including telomeres. However, as telomeres are also mainly involved in aging, any possible interaction between the two would be worth noting, especially as telomere dysfunction also contributes to cancer and other age-related diseases. Ascertaining the balance between degeneration and cancer development is crucial in cell biology, in which telomeres function as a key regulator between the two extremes. The essential roles that EMT and telomere protection have in aging reveal a potential mutual interaction that has not yet been explored, and which could be used in disease therapy. In this review, the known functions of EMT and telomeres in aging are discussed and their potential interaction in age-related diseases is highlighted.
    Matched MeSH terms: Extracellular Matrix
  18. Loke, C.Y., Nur Hidayah, M.S., Mohd Fadhli, M.F., Teo, SK, Nor Hidayah, A.G., Yasmin Anum, M.Y., et al.
    Medicine & Health, 2010;5(1):1-12.
    MyJurnal
    Chlorella vulgaris, a unicellular microalgae, produces many intracellular phytochemicals namely carotenoids, tocopherols, ubiquinone and protein. Skin ageing which is induced by oxidative stress involves decreased extracellular matrix synthesis and increased expression of enzymes that degrade the collagenous matrix. The objective of this study was to determine the effect of C. vulgaris on the expression of genes encoded for collagen (COL) and matrix metalloproteinases (MMPs) which are involved in skin ageing. Human diploid fibroblasts (HDFs) were obtained from circumcision foreskin of 8-12 year-old boys. HDFs were cultured into 3 groups: untreated control cells, cells with stress-induced premature senescence (SIPS; cells were induced with H2O2 at passage 6 for 2 weeks) and SIPS treated with C. vulgaris (prolonged C. vulgaris treatment started at passage 4 and combined treatment with H2O2 at passage 6 for 2 weeks). Senescence-associated ß-galactosidase (SA ß-gal) was determined using senescent cells histochemical staining kit (Sigma, USA). Expression of COLI, COLIII, COLIV, MMPI, MMPII and MMPIII genes was quantitatively analysed with real-time RT-PCR method (iScript™ One Step real-time PCR with SYBR® Green; Biorad). HDFs treated with H2O2 (SIPS) exhibited senescent morphological features of flattening and enlarged with increased expression of SA ß-gal (p
    Matched MeSH terms: Extracellular Matrix
  19. Larsson HM, Vythilingam G, Pinnagoda K, Vardar E, Engelhardt EM, Sothilingam S, et al.
    Sci Rep, 2018 07 03;8(1):10057.
    PMID: 29968749 DOI: 10.1038/s41598-018-27621-9
    There is a need for efficient and "off-the-shelf" grafts in urethral reconstructive surgery. Currently available surgical techniques require harvesting of grafts from autologous sites, with increased risk of surgical complications and added patient discomfort. Therefore, a cost-effective and cell-free graft with adequate regenerative potential has a great chance to be translated into clinical practice. Tubular cell-free collagen grafts were prepared by varying the collagen density and fiber distribution, thereby creating a polarized low fiber density collagen graft (LD-graft). A uniform, high fiber density collagen graft (HD-graft) was engineered as a control. These two grafts were implanted to bridge a 2 cm long iatrogenic urethral defect in a rabbit model. Histology revealed that rabbits implanted with the LD-graft had a better smooth muscle regeneration compared to the HD-graft. The overall functional outcome assessed by contrast voiding cystourethrography showed patency of the urethra in 90% for the LD-graft and in 66.6% for the HD-graft. Functional regeneration of the rabbit implanted with the LD-graft could further be demonstrated by successful mating, resulting in healthy offspring. In conclusion, cell-free low-density polarized collagen grafts show better urethral regeneration than high-density collagen grafts.
    Matched MeSH terms: Extracellular Matrix
  20. Abid Nordin, Shiplu Roy Chowdhury, Ruszymah Idrus, Aminuddin Saim
    Sains Malaysiana, 2018;47:2463-2471.
    Skin wound healing is a complex physiological event, involving many cellular and molecular components. The event of
    wound healing is the coordinated overlap of a number of distinct phases, namely haemostasis, inflammatory, proliferative
    and remodelling. The molecular events surrounding wound healing, particularly the reepithelialisation, has been reported
    to be similar to the epithelial to mesenchymal transition (EMT). In this review, the mechanism between epithelialisation
    and EMT were compared. Both are characterised by the loss of epithelial integrity and increased motility. In terms of
    the signalling kinases, Smad and mitogen-activated protein kinase (MAPK) has been reported to be involved in both
    reepithelialisation and EMT. At the transcriptional level, SLUG transcription factor has been reported to be important for
    both reepithelialisation and EMT. Extracellular matrix proteins that have been associated with both events are collagen
    and laminin. Lastly, both events required the interplay between matrix metalloproteinases (MMPs) and its inhibitor. As a
    conclusion, both reepithelialisation and EMT shares similar signaling cascade and transcriptional regulation to exhibit
    decreased epithelial traits and increased motility in keratinocytes.
    Matched MeSH terms: Extracellular Matrix Proteins
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