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

Abstract

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.

MiR‐4756 promotes albumin‐induced renal tubular epithelial cell epithelial‐to‐mesenchymal transition and endoplasmic reticulum stress via targeting Sestrin2

“…In our previous research, we demonstrated that ERK1/2 plays an important role in regulating renal tubular epithelial cell EMT processes (Zheng et al, ). In this study, we found that the miR‐4756 mimic significantly increased ERK1/2 phosphorylation in the presence of HSA.…”

The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells

“…MicroRNAs (miRNAs) are short noncoding RNAs that modulate fundamental cellular processes, and existed researches showed several miRNAs are highly associated with the EMT, such as miR‐30c, miR‐23a/b, miR‐130b, and miR‐302 family (Bai, Geng, Zhou, Tian, & Li, ; Lipchina, Elkabetz, & Hafner, ; Liu et al, ; Zhao, Yin, & Li, ; Zheng, Guan, & Jia, ). Among them, miR‐302 family, including miR‐302a, miR‐302b, miR‐302c, and miR‐302d, are located on human chromosome 4q25.…”

Renoprotective effects of brown adipose tissue activation in diabetic mice

“…Real‐time quantitative polymerase chain reaction (qPCR) was performed in a Roche Lightcycler 480II (Roche, Basle, Switzerland) using a SYBR Green qPCR Kit (Takara). Relative gene expression was calculated using the 2 −ΔΔCt method and 18 s as an internal control . The primers used are listed in Table .…”

“…Relative gene expression was calculated using the 2 −ΔΔCt method and 18 s as an internal control. 16 The primers used are listed in Table 1.…”