The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy

Research output: Contribution to journalJournal articlepeer-review

  • Zongji Zheng
  • Meiping Guan
  • Yijie Jia
  • Dan Wang
  • Ruoyu Pang
  • Fuping Lv
  • Zhizhou Xiao
  • Ling Wang
  • Hongbin Zhang
  • Yaoming Xue

MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 suppressed miR-26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E cells, and these changes were also found in the kidney cortex of 40-week-old diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Bioinformatic analyses and luciferase assays further demonstrated that both miR-26a and miR-30c targeted connective tissue growth factor (CTGF); additionally, Snail family zinc finger 1 (Snail1), a potent epithelial-to-mesenchymal transition (EMT) inducer, was targeted by miR-30c. Overexpression of miR-26a and miR-30c coordinately decreased CTGF protein levels and subsequently ameliorated TGFβ1-induced EMT in NRK-52E cells. Co-silencing of miR-26a and miR-30c exhibited the opposite effect. Moreover, miR-26a and miR-30c co-silenced CTGF to decrease ERK1/2 and p38 MAPK activation. Furthermore, miR-26a was up-regulated in urinary extracellular vesicles of diabetic nephropathy patients. Our study provides evidence for the cooperative roles of miR-26a and miR-30c in the pathogenesis of diabetic nephropathy, and the co-targeting of miR-26a and miR-30c could provide a new direction for diabetic nephropathy treatment.

Original languageEnglish
Article number37492
JournalScientific Reports
Volume6
Number of pages12
ISSN2045-2322
DOIs
Publication statusPublished - 22 Nov 2016

Number of downloads are based on statistics from Google Scholar and www.ku.dk


No data available

ID: 172394883