miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy.
Yingchun ZhuJiang XuWenxing LiangJi LiLinhong FengPengXi ZhengTingting JiShou-Jun BaiPublished in: International journal of endocrinology (2019)
Recently, microRNAs have been recognized as crucial regulators of diabetic nephropathy (DN) development. Epithelial-to-mesenchymal transition (EMT) can play a significant role in tubulointerstitial fibrosis, and it is a hallmark of diabetic nephropathy progression. Nevertheless, the function of miR-98-5p in the modulation of EMT and renal fibrosis during DN remains barely investigated. Hence, identifying the mechanisms of miR-98-5p in regulating EMT and fibrosis is of huge significance. In our present research, decreased miR-98-5p was demonstrated in db/db mice and mice mesangial cells treated with the high dose of glucose. Meanwhile, activated EMT and increased fibrosis was accompanied with the decrease of miR-98-5p in vitro and in vivo. Additionally, to further find out the roles of miR-98-5p in DN development, overexpression of miR-98-5p was applied. Firstly, in vivo investigation exhibited that elevation of miR-98-5p restrained proteinuria, serum creatinine, BUN, the EMT process, and fibrosis. Furthermore, high glucose was able to promote mice mesangial cell proliferation, EMT process, and induced renal fibrosis, which could be prevented by overexpression of miR-98-5p. Moreover, high mobility group A (HMGA2) can exhibit an important role in diverse biological processes. Here, HMGA2 was investigated as a target of miR-98-5p currently. Luciferase reporter assay was conducted and the correlation of miR-98-5p and HMGA2 was validated. Moreover, it was displayed that HMGA2 was remarkably elevated in db/db mice and mice mesangial cells. Furthermore, miR-98-5p strongly depressed HMGA2 protein and mRNA levels in mice mesangial cells. Overall, these revealed miR-98-5p could suppress the EMT process and renal fibrosis through targeting HMGA2 in DN.
Keyphrases
- diabetic nephropathy
- high glucose
- epithelial mesenchymal transition
- cell proliferation
- high fat diet induced
- induced apoptosis
- endothelial cells
- high dose
- cancer therapy
- mass spectrometry
- wild type
- high throughput
- low dose
- small molecule
- oxidative stress
- insulin resistance
- cell death
- adipose tissue
- cell cycle
- uric acid
- stem cell transplantation
- diabetic rats
- newly diagnosed
- amino acid