Hepatic Stellate Cell Selective Disruption of Dynamin-2 GTPase Increases Murine Fibrogenesis through Up-Regulation of Sphingosine-1 Phosphate-Induced Cell Migration.

ABSTRACT: Dynamin-2 (Dyn2) is implicated in endocytosis of receptor tyrosine kinases, which contribute to hepatic stellate cell (HSC) activation and liver fibrosis. A point mutation converting lysine 44 of Dyn2 to alanine (Dyn2K44A) disrupts its GTPase activity. We hypothesized that Dyn2K44A expression in HSCs would decrease HSC activation and fibrogenesis in vivo by disrupting receptor tyrosine kinase endocytosis and signaling. Dyn2K44A^fl/fl mice were crossed with Collagen1-Cre (Col1^Cre) mice to generate offspring with HSC selective expression of Dyn2K44A (Col1^Cre/Dyn2K44A^fl/fl). Contrary to our hypothesis, Col1^Cre/Dyn2K44A^fl/fl mice showed increased hepatic fibrosis in response to liver injury. To elucidate mechanisms, we conducted

SUBMITTER: Wang R 

PROVIDER: S-EPMC5225297 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature