The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy
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The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy. / Zheng, Zongji; Guan, Meiping; Jia, Yijie; Wang, Dan; Pang, Ruoyu; Lv, Fuping; Xiao, Zhizhou; Wang, Ling; Zhang, Hongbin; Xue, Yaoming.
In: Scientific Reports, Vol. 6, 37492, 22.11.2016.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy
AU - Zheng, Zongji
AU - Guan, Meiping
AU - Jia, Yijie
AU - Wang, Dan
AU - Pang, Ruoyu
AU - Lv, Fuping
AU - Xiao, Zhizhou
AU - Wang, Ling
AU - Zhang, Hongbin
AU - Xue, Yaoming
PY - 2016/11/22
Y1 - 2016/11/22
N2 - 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.
AB - 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.
U2 - 10.1038/srep37492
DO - 10.1038/srep37492
M3 - Journal article
C2 - 27874055
VL - 6
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 37492
ER -
ID: 172394883