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The hepatocyte growth factor/c-met pathway is a key determinant of the fibrotic kidney local microenvironment.
- Source :
-
IScience [iScience] 2021 Sep 09; Vol. 24 (10), pp. 103112. Date of Electronic Publication: 2021 Sep 09 (Print Publication: 2021). - Publication Year :
- 2021
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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 influences epithelial plasticity, myofibroblast activation, and extracellular matrix synthesis/degradation, which ultimately determined the characteristics of the fibrotic KLM. Our findings open the possibility of designing effective therapeutic strategies to retard CKD.<br />Competing Interests: The authors declare no conflict of interest.<br /> (© 2021 The Authors.)
Details
- Language :
- English
- ISSN :
- 2589-0042
- Volume :
- 24
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- IScience
- Publication Type :
- Academic Journal
- Accession number :
- 34622165
- Full Text :
- https://doi.org/10.1016/j.isci.2021.103112