Interplay of Matrix Stiffness and c-SRC in Hepatic Fibrosis.

摘要: Introduction: In liver fibrosis activation of hepatic stellate cells (HSC) comprises phenotypical change into profibrotic and myofibroplastic with increased contraction secretion extracellular matrix (ECM) proteins. The small GTPase RhoA orchestrates cytoskeleton formation, migration mobility via non-receptor tyrosine-protein kinase c-SRC (cellular sarcoma) in different cells. Furthermore, its downstream effector Rho-kinase also play a crucial role fibrogenesis. Matrix stiffness promotes HSC modulation. This study investigated the interaction under conditions. Methods: Liver was induced rats using bile duct ligation (BDL), thioacetamide (TAA) or carbon tetrachloride (CCl4) models. mRNA levels albumin, PDGF-R, RHOA, COL1A1 αSMA were analyzed qRT-PCR. Western Blots phospho-specific antibodies against p-c-SRC418 p-c-SRC530 activating inactivating respectively. LX2 hepatocytes cultured on acrylamide gels 1kPa 12kPa plastic to mimic non-fibrotic, fibrotic cirrhotic environments, then exposed SRC-inhibitor PP2. Overexpression performed by transfection RhoA-plasmids. Additionally, samples from patients controls collected at transplantations tumor resections for protein expression Blot. Results: Transcription albumin decreased, whereas transcription compared gels. showed upregulation levels. Inhibition PP2 led an increase most prominently overexpression, inhibition failed improve fibrosis. significantly elevated human experimental fibrosis, while inactivated. Conclusions: shows that is inactive activated myofibroblast-like cirrhosis. Inactivation mediated crosstalk upon cell progression.