| First Author | Fu H | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 10 | Pages | 103112 |
| PubMed ID | 34622165 | Mgi Jnum | J:313605 |
| Mgi Id | MGI:6790544 | Doi | 10.1016/j.isci.2021.103112 |
| Citation | Fu H, et al. (2021) The hepatocyte growth factor/c-met pathway is a key determinant of the fibrotic kidney local microenvironment. iScience 24(10):103112 |
| abstractText | 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. |
