The Nereidid worm is a marine polychaete commonly found near the Nipa palm (Nypa fructicans) along the mangrove estuary. Recently, many usages have been documented for this polychaete family. Nevertheless, the true potentials of these marine worms, especially Namalycastis sp., from the medical perspective are still unknown. The current study investigated the cytotoxicity effect of Namalycastis sp. crude extracts on mice 3T3 fibroblast cells and human lung MRC-5 fibroblast cells. Thirteen concentrations (2, 4, 8, 16, 31, 63 µg/mL and 0.1, 0.3, 0.5, 1, 2, 4, 8 mg/mL) of the extracts were used as a treatment for 24 h, and cell viability was measured via the MTT assay. None of the 13 concentrations of Namalycastis sp. crude extracts showed cytotoxicity effects on the cell types investigated. However, based on the live images captured by the IncuCyte™ imaging system, the cells treated with Namalycastis sp. crude extracts showed an increased proliferation and growth rate in less than 10 h Furthermore, the extract concentration of 8 µg/mL induced the highest cell proliferation rate whereas 8 mg/mL led to the lowest cell proliferation rate following the treatment. Overall, Namalycastis sp. crude extracts were non-toxic on mice and human cells within the tested concentrations set. Still, it increased cell viability and proliferation compared with the control. This finding could pave the way for an alternative therapeutic strategy to treat debilitating disorders such as ageing, cardiovascular diseases, and neurodegenerative diseases.
Elevated circulating hepcidin levels have been reported in patients with pulmonary artery hypertension (PAH). Hepcidin has been shown to promote proliferation of human pulmonary artery smooth muscle cells (PASMCs) in vitro, suggesting a potential role in PAH pathogenesis. However, the role of human pulmonary artery endothelial cells (PAECs) as either a source of hepcidin, or the effect of hepcidin on PAEC function is not as well described. The objective of this study was to define the role of the hepcidin-ferroportin axis on the phenotype of PAEC and to study potential PAEC-PASMC interactions relevant to the pathogenesis of pulmonary vascular remodeling and PAH. PAECs treated with hepcidin, or interleukin-6 were investigated for both ferroportin and hepcidin release and regulation using immunofluorescence, mRNA levels and cellular release assays. Effects of hepcidin on PASMC and PAEC mitochondrial function was investigated using immunofluorescence and seahorse assay. Migration and proliferation of PASMCs treated with conditioned media from hPAEC treated with hepcidin was investigated using the xCELLigence system and other tools. We demonstrate in this study that PAECs express ferroportin; hepcidin treatment of PAECs resulted in mitochondrial iron accumulation and intracellular hepcidin biosynthesis and release. Conditioned media from hepcidin treated PAECs caused PASMCs to down-regulate ferroportin expression whilst promoting migration and proliferation. Inhibition of hepcidin in PAEC conditioned media limited these responses. PASMC cellular and mitochondrial iron retention are associated with migratory and proliferative responses. This study confirms that the hepcidin ferroportin axis is present and operational in PAECs. Modulation of this axis shows distinct differences in responses seen between PAECS and PASMCs. Stimulation of this axis in PAECs with hepcidin may well institute proliferative and migratory responses in PASMCs of relevance to pathogenesis of PAH offering potential novel therapeutic targets.