Ca^(2+)/钙调蛋白依赖性蛋白激酶Ⅱ在PDGF诱导肝星状细胞胶原合成中的作用  

Effects of Ca^(2+)/calmodulin-dependent protein kinase Ⅱ on PDGF-induced collagen α1(Ⅰ) production in human hepatic stellate cells

作　　者：安萍[1] 刘亚玲[1] 全晓静[1] 刘璐[1] 罗和生[1] 

机构地区：[1]武汉大学人民医院消化内科,湖北武汉430060

出　　处：《胃肠病学和肝病学杂志》2013年第1期10-12,共3页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的观察Ca2+/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)对PDGF诱导下人肝星状细胞(hepatic stellate cell,HSC)colla-genα1(Ⅰ)合成的影响。方法 CaMKⅡαsiRNA转染对HSC内CaMKⅡα进行干扰,real-time PCR法检测HSC collagenα1(Ⅰ)及TIMP-1 mRNA的表达,Western blot法检测collagenα1(Ⅰ)及MMP-2、TIMP-1表达的变化,ELISA法检测HSC collagenα1(Ⅰ)分泌的变化。结果 CaMKⅡαsiRNA可显著抑制PDGF诱导下HSC collagenα1(Ⅰ)及MMP-2、TIMP-1的转录、蛋白表达以及collagenα1(Ⅰ)的分泌,差异均有统计学意义(P<0.05)。结论 CaMKⅡα信号参与了PDGF诱导下HSC collagenα1(Ⅰ)的产生与分泌,同时通过抑制MMP-2、促进TIMP-1的表达而阻止胶原的降解,是肝纤维化发展过程中PDGF信号的重要调控分子和肝纤维化的潜在治疗靶点。To observe the effects of Ca^2＋/calmOdulin-dependent protein kinase Ⅱ （ CaMK Ⅱ ） on PDGF-induced collagen α1 （ Ⅰ） production in human hepatic stellate cells. Methods The knockdown of CaMK Ⅱ a was performed by CaMK Ⅱ α siRNA transient transfection. The mRNA and protein expression of collagen α1 （Ⅰ） , MMP-2 and TIMP-1 were determined by real-time PCR and Western blot, respectively. The secretion of collagen α1 （Ⅰ） in culture media was tested by ELISA. Results CaMK H knockdown by CaMK Ⅱ α siRNA significantly inhibited collagen α1（Ⅰ） expression and secretion in PDGF-induced HSCs. CaMK Ⅱ inhibition resulted in up-regulation of MMP-2 and down-regulation of TIMP-1. Conclusion CaMK Ⅱ a regulate PDGF-induced collagen α1 （Ⅰ） production and secretion, increase TIMP-1 expression and decrease MMP-2 expression. Our study shed light on CaMK Ⅱ as a crucial signal in PDGF-activated HSCs and a potential therapeutic target in hepatic fibrosis.

关 键 词：CA^2+ 钙调蛋白依赖性蛋白激酶Ⅱ 肝星状细胞 血小板源性生长因子 胶原 基质金属蛋白酶组织抑制因子-1 

分 类 号：R575[医药卫生—消化系统]