Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, PR China.
FEBS Lett. 2010 Feb 19;584(4):811-6. doi: 10.1016/j.febslet.2009.12.053. Epub 2010 Jan 12.
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.
在糖尿病肾病中，近端肾小管细胞（PTC）中胶原蛋白 IV 的沉积起着重要作用，但胶原蛋白 IV 过度产生的机制仍知之甚少。在这项研究中，我们检查了 HK-2 细胞的 miRNA 谱，发现高糖/TGF-β1 诱导 miR-29a 的显著下调。然后我们表明，miR-29a 通过直接靶向 col4a1 和 col4a2 的 3'UTRs 负调控胶原蛋白 IV。这些结果表明，miR-29a 作为一种抑制剂来精细调节胶原蛋白的表达，而高糖引起的 miR-29a 减少可能会增加 PTC 中过量胶原蛋白沉积的风险。
