AUTHOR=Zhang Yanhong , Yin Nina , Sun Anbang , Wu Qifang , Hu Wenzhu , Hou Xin , Zeng Xixi , Zhu Min , Liao Yanhong 

TITLE=Transient Receptor Potential Channel 6 Knockout Ameliorates Kidney Fibrosis by Inhibition of Epithelial–Mesenchymal Transition

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 8 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.602703

DOI=10.3389/fcell.2020.602703

ISSN=2296-634X

ABSTRACT=Kidney fibrosis is generally confirmed to a significant role in chronic kidney disease resulting in the end-stage kidney failure. Epithelial-mesenchymal transition (EMT) is an important molecular mechanism contributing to fibrosis. Tubular epithelial cells (TEC), the major component of kidney parenchyma, are vulnerable to different types of injuries and as a significant source of myofibroblast by EMT. Furthermore, TRPC6 knockout plays an anti-fibrotic role in ameliorating kidney damage. However, the relationship between TRPC6 and EMT is unknown. In this study, TRPC6-/- and WT mice were subjected to a unilateral ureteric obstruction (UUO) operation. Primary TEC were treated with TGF-β1. Western blot and immunofluorescence data showed that fibrotic injuries alleviated with the inhibition of EMT in TRPC6 -/-  mice compared to that of WT mice. The activation of AKT-mTOR and ERK1/2 pathways was down-regulated in the TRPC6-/- mice, while the loss of Na+/K+-ATPase and APQ1 was partially recovered. We conclude that TRPC6 knockout may ameliorate kidney fibrosis by inhibition of EMT through down-regulating the AKT-mTOR and ERK1/2 pathways. This could contribute to the development of effective therapeutic strategies on chronic kidney diseases.