All (angiotensin II) is a vasoactive peptide that plays an important role in the development of liver fibrosis mainly by regulating profibrotic cytokine expression such as TGF-beta (transforming growth factor-beta). Activated HSCs (hepatic stellate cells) are the major cell type responsible for ECM (extracellular matrix) deposition during liver fibrosis and are also a target for All and TGF-beta actions. Here, we studied the effect of All on the mRNA levels of TGF-beta isoforms in primary cultures of rat HSCs. Both quiescent and activated HSCs were stimulated with All for different time periods, and mRNA levels of TGF-beta 1, TGF-beta 2 and TGF-beta 3 isoforms were evaluated using RNasel protection assay. The mRNA levels of all TGF-beta isoforms, particularly TGF-beta 2 and TGF-beta 3, were increased after All treatment in activated HSCs. In addition, activated HSCs were able to produce active TGF-beta protein after All treatment. The mRNA expression of TGF-beta isoforms induced by All required both ERK1/2 and Nox (NADPH oxidase) activation but not PKC (protein kinase C) participation. ERK1/2 activation induced by All occurs via AT1 receptors, but independently of either PKC and Nox activation or EGFR (epidermal growth factor receptor) transactivation. Interestingly, All has a similar effect on TGF-beta expression in quiescent HSCs, although it has a smaller but significant effect on ERK1/2 activation in these cells.
Última actualización: 18/06/2018