{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:32:06Z","timestamp":1768519926190,"version":"3.49.0"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T00:00:00Z","timestamp":1331596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold> Hepatic stellate cells (HSC) are the major players in hepatic fibrosis. As a most potent mitogen, transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) strongly activates HSC and increases intracellular Ca<jats:sup>2+<\/jats:sup> concentration. Here, we assessed the potential role of Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent protein kinase II (CaMKII), a main downstream effector of the Ca<jats:sup>2+<\/jats:sup> signal in liver fibrogenesis cascade.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> A human immortal HSC cell line, LX\u20102, and primary rat hepatic stellate cells were used in current study. CaMKII blockage and Akt inhibition were performed by KN\u201093\/CaMKII\u03b1 siRNA and LY294002, respectively. HSC proliferation was detected by 5\u2010bromodeoxyuridine incorporation assay. Real\u2010time polymerase chain reaction, western blot and enzyme\u2010linked immunosorbent assay were used to measure mRNA, cellular protein and protein in medium, respectively. Procollagen \u03b11(I) expression was detected by immunocytochemistry. The role of CaMKII on TGF\u2010\u03b2\/Smad\u2010induced collagen \u03b11(I) expression was determined by (CAGA)<jats:sub>12<\/jats:sub>\u2010MLP luciferase activity assay.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> TGF\u2010\u03b2 dramatically increased CaMKII mRNA, and total and phosphorylated CaMKII expression. KN\u201093 and CaMKII\u03b1 siRNA suppressed TGF\u2010\u03b2\u2010mediated HSC proliferation. CaMKII interruption blocked TGF\u2010\u03b2\u2010elicited Akt activation. LY294002 arrested HSC proliferation and collagen \u03b11(I) production but had no effect on CaMKII. Furthermore, CaMKII led to increased p21 and p27 expression. KN\u201093 and CaMKII\u03b1 siRNA inhibited TGF\u2010\u03b2\u2010induced and basal collagen \u03b11(I) production but had no effect on the activity of (CAGA)<jats:sub>12<\/jats:sub>\u2010MLP luciferase in response to TGF\u2010\u03b2 stimulation.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> CaMKII is a pivotal signal in TGF\u2010\u03b2\u2010induced fibrogenic cascades by means of stimulating HSC proliferation, and involved in a basal collagen production. Therefore, CaMKII will be a potentially effective target in the development of therapeutic intervention strategies to attenuate hepatic fibrosis.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2012.00983.x","type":"journal-article","created":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T11:43:32Z","timestamp":1330429412000},"page":"806-818","source":"Crossref","is-referenced-by-count":14,"title":["Ca<sup>2+<\/sup>\/calmodulin\u2010 dependent protein kinase II mediates transforming growth factor\u2010\u03b2\u2010induced hepatic stellate cells proliferation but not in collagen \u03b11(I) 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