The hepatocyte growth factor/c-met pathway is a key determinant of the fibrotic kidney local microenvironment.

ABSTRACT: The kidney local microenvironment (KLM) plays a critical role in the pathogenesis of kidney fibrosis. However, the composition and regulation of a fibrotic KLM remain unclear. Through a multidisciplinary approach, we investigated the roles of the hepatocyte growth factor/c-met signaling pathway in regulating KLM formation in various chronic kidney disease (CKD) models. We performed a retrospective analysis of single-cell RNA sequencing data and determined that tubular epithelial cells and macrophages are two major cell populations in a fibrotic kidney. We then created a mathematical model that predicted loss of c-met in tubular cells would cause greater responses to injury than loss of c-met in macrophages. By generating c-met conditional knockout mice, we validated that loss of c-met infl

SUBMITTER: Fu H 

PROVIDER: S-EPMC8479790 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature