K+‐channel inhibition reduces portal perfusion pressure in fibrotic rats and fibrosis associated characteristics of hepatic stellate cells

• DOI: 10.1111/liv.12681
• Publication Date: 2014-09-11T16:31:36Z
• Authors: Christian Freise; Silke Heldwein; Ulrike Erben; Joachim Hoyer; Ralf Köhler; Korinna Jöhrens; Eleonora Patsenker; Martin Ruehl; Daniel Seehofer; Felix Stickel; Rajan Somasundaram
• Keywords: Hepatic stellate cell; Hepatic fibrosis

In liver fibrosis, activated hepatic stellate cells (HSC) secrete excess extracellular matrix, thus, represent key targets for antifibrotic treatment strategies. Intermediate-conductance Ca(2) (+) -activated K(+) -channels (KCa3.1) are expressed in non-excitable tissues affecting proliferation, migration and vascular resistance rendering KCa3.1 potential fibrosis. So far, no information about expression their role HSC exists. Aim was to quantify the depending on activation investigation of properties specific inhibitor TRAM-34 vitro vivo. functionality were studied TGF-β1-activated by quantitative real time PCR, western-blot patch-clamp analysis respectively. Effects cell cycle fibrosis-related gene assessed [(3) H]-thymidine incorporation, FACS-analysis RT-PCR vivo, protein determined bile duct ligated rats situ perfusion, Taqman PCR immunohistochemistry Fibrotic exhibited higher KCa3.1-expressions than normal tissue untreated cells. inhibition with reduced proliferation induction arrest TGF-β1-induced collagen I, alpha-smooth muscle actin TGF-β1 itself. Furthermore, blocked TGF-β signalling HSC. thromboxane agonist-induced portal perfusion pressure. Inhibition downregulates fibrosis-associated vitro, reduces pressure Thus, may novel