High glucose down-regulates miR-29a to increase collagen IV production in HK-2 cells.

Deposition of collagen IV in proximal tubule cells (PTCs) plays an important role during diabetic nephropathy, but the mechanism underlying excessive production of collagen IV remains poorly understood. In this study, we examined the miRNA profile of HK-2 cells and found that high glucose/TGF-beta1 induced significant down-regulation of miR-29a. We then showed that miR-29a negatively regulated collagen IV by directly targeting the 3'UTRs of col4a1 and col4a2. These results suggest that miR-29a acts as a repressor to fine-tune collagen expression and that the reduction of miR-29a caused by high glucose may increase the risk of excess collagen deposition in PTCs. Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.