Chintalgattu Vishnu, Katwa Laxmansa C
Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Biochem Biophys Res Commun. 2009 Sep 4;386(4):612-6. doi: 10.1016/j.bbrc.2009.06.076. Epub 2009 Jun 18.
Previous studies have demonstrated a role for angiotensin II (AngII) and myofibroblasts (myoFb) in cardiac fibrosis. However, the role of PKC-delta in AngII mediated cardiac fibrosis is unclear. Therefore, the present study was designed to investigate the role of PKC-delta in AngII induced cardiac collagen expression and fibrosis. AngII treatment significantly (p<0.05) increased myoFb collagen expression, whereas PKC-delta siRNA treatment or rottlerin, a PKC-delta inhibitor abrogated (p<0.05) AngII induced collagen expression. MyoFb transfected with PKC-delta over expression vector showed significant increase (p<0.05) in the collagen expression as compared to control. Two weeks of chronic AngII infused rats showed significant (p<0.05) increase in collagen expression compared to sham operated rats. This increase in cardiac collagen expression was abrogated by rottlerin treatment. In conclusion, both in vitro and in vivo data strongly suggest a role for PKC-delta in AngII induced cardiac fibrosis.
先前的研究已经证明血管紧张素II(AngII)和成肌纤维细胞(myoFb)在心脏纤维化中起作用。然而,蛋白激酶Cδ(PKC-δ)在AngII介导的心脏纤维化中的作用尚不清楚。因此,本研究旨在探讨PKC-δ在AngII诱导的心脏胶原表达和纤维化中的作用。AngII处理显著(p<0.05)增加了成肌纤维细胞的胶原表达,而PKC-δ小干扰RNA处理或PKC-δ抑制剂rottlerin消除了(p<0.05)AngII诱导的胶原表达。与对照相比,用PKC-δ过表达载体转染的成肌纤维细胞显示胶原表达显著增加(p<0.05)。与假手术大鼠相比,慢性输注AngII两周的大鼠胶原表达显著增加(p<0.05)。rottlerin处理消除了心脏胶原表达的这种增加。总之,体外和体内数据均强烈表明PKC-δ在AngII诱导的心脏纤维化中起作用。