Upregulation of Megalin, Cubilin, NGAL mRNA expression in kidney may represent tubular injury and apoptosis in chronic condition of rat diabetic model

INTRODUCTION: Diabetes mellitus (DM) leads to microvascular injury development and produces diabetes nephropathy (DN) with proteinuria, tubular injury, apoptosis and autophagy with upregulation of Bax, BASP and mTORC-1. Megalin, Cubilin and Neutrophil Gelatinase Associated Lipocalin (NGAL) play role in acute pathological condition of kidney injury, however its expression in chronic and slowly progressive kidney injury such as DN has not been elucidated yet. This study focuses upregulation of Megalin, Cubilin and NGAL in association with tubular injury and apoptosis in DN condition.

MATERIALS AND METHODS: Diabetic condition was performed with intraperitoneal injection of Streptozotocin 60 mg/kg body weight (BW) in Sprague Dawley rats (2 months old, n=24), and were kept for 1, 2, and 4 months (DM1, DM2, and DM4, respectively). Control group was injected with NaCl 0.9%. Serum glucose level and proteinuria score were assessed, furthermore tubular injury score was quantified based on Periodic-Acid Schiff (PAS) staining. Reverse Transcriptase-PCR (RT-PCR) was carried out for NGAL, Megalin, Cubilin, m-TOR, Bax, and BASP-1 mRNA expression. Data were analyzed using SPSS 22 software.

RESULTS: DM led to kidney injury in this model with significant higher glucose level, proteinuria and tubular injury, especially in DM4 group which represented chronic phase of DN and CKD. These findings associated with upregulation of Megalin,Cubilin and NGAL mRNA expression in DM groups, especially in DM4 group. DM4 group also revealed higher expression of Bax, BASP and mTOR mRNA expression which demonstrated apoptosis.

CONCLUSION: Megalin, Cubilin and NGAL upregulation may represent tubular injury and apoptosis as progression of DN.