Overexpression of TGF- β1 induces renal fibrosis and accelerates the decline in kidney function in polycystic kidney disease.

Overexpression of TGF-β1 induces renal fibrosis and accelerates the decline in kidney function in polycystic kidney disease. Am J Physiol Renal Physiol. 2020 Nov 09;: Authors: Zhang Y, Dai Y, Raman A, Daniel E, Metcalf J, Reif GA, Pierucci-Alves F, Wallace DP Abstract Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of numerous fluid-filled cysts, extensive fibrosis, and the progressive decline in kidney function. Transforming growth factor β1 (TGF-β1), an important mediator for renal fibrosis and chronic kidney disease, is overexpressed by cystic cells compared to normal kidney cells; however, its role in PKD pathogenesis remains undefined. To investigate the effect of TGF-β1 on cyst growth, fibrosis, and disease progression, we overexpressed active TGF-β1 specifically in collecting duct (CD)s of phenotypic normal (Pkd1RC/+) and Pkd1RC/RC mice. In normal mice, CD-specific TGF-β1 overexpression caused tubule dilations by 5 weeks of age that were accompanied by increased levels of phosphorylated SMAD3, α-smooth muscle actin, vimentin, and periostin; however, it did not induce overt cyst formation by 20 weeks. In Pkd1RC/RCmice, CD overexpression of TGF-β1 increased cyst epithelial cell proliferation. However, extensive fibrosis limited cyst enlargement and caused contraction of the kidneys, leading to a loss of renal function and a shortened lifespan of the mice. These data demonstrate that ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research