AUTHOR=Huang Huiya , Huang Xiaozhong , Luo Shengnan , Zhang Huidi , Hu Feifei , Chen Ruyi , Huang Chaoxing , Su Zhen 

TITLE=The MicroRNA MiR-29c Alleviates Renal Fibrosis via TPM1-Mediated Suppression of the Wnt/β-Catenin Pathway

JOURNAL=Frontiers in Physiology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00331

DOI=10.3389/fphys.2020.00331

ISSN=1664-042X

ABSTRACT=Purpose: This study aimed to evaluate the mechanism by which miR-29c expression in fibroblasts regulates renal interstitial fibrosis. 
Methods: We stimulated NRK-49F cells with TGF-β1 to mimic the effects of fibrosis in vitro, while unilateral ureteral obstruction (UUO) was performed to obstruct the mid-ureter in mice. MiR-29c mimic or miR-29c inhibitor was used to mediate genes expressions in vitro. The recombinant adeno associated virus (rAAV) vectors carrying a FSP1 promoter that encodes miR-29c precursor or miR-29c inhibitor was used to mediate genes expressions in vivo, and a flank incision was made to expose the left kidney of each animal. 
Results: In the present study, TGF-β1 was demonstrated to regulate miR-29c expression through Wnt/β-catenin signaling. In contrast, miR-29c appears to inhibit the Wnt/β-catenin pathway by suppressing TPM1 expression. As suggested by this feedback mechanism, miR-29c may be a key fibrosis-related microRNA expressed by fibroblasts in TGF-β1/Wnt/β-catenin-driven renal fibrosis, and manipulation of miR-29c action may accordingly offer a potential therapeutic pathway for renal fibrosis treatment.
Conclusion: MiR-29c expression was downregulated in UUO mouse kidneys as well as TGF-β1-treated NRK-49F cells, which thus inhibits myofibroblast formation via targeting of TPM1. Additionally, the production of extracellular matrix in renal fibroblasts appears to be controlled by the reciprocal regulation of miR-29c action and the Wnt/β-catenin pathway.