Do Calcium Activated Potassium Channels Control Proliferation of Myofibroblasts? Implications for Fibroproliferative Diseases

摘要

E The calcium-activated K+ channel, KCa3.1, has an important function in Ca2+ signaling for maintaining a negative membrane potential, which provides an electrochemical gradient to drive Ca2+ influx. In fibroblasts this channel is up-regulated in a TGF-J3 dependent manner. The same TGF-p / SMAD signaling is increased in several fibroproliferative diseases, for example in kidney fibrosis [Grgic et al 2009], or Dupuytren's disease [Krause et al 2011 ]. This pathway is also found to be involved in chronic inflammatory autoimmune diseases, like diabetes type 1 and T-cell mediated colitis or multiple sclerosis. Blockage of KCa 3.1 in fibroblast can suppress myogenesis [Pena 2000] and in pancreatic cancer cell lines it can stop proliferation [Jager et al 2004]: