Tang Hong-Tai, Cheng Da-Sheng, Jia Yi-Tao, Ben Dao-Feng, Ma Bing, Lv Kai-Yang, Wei Duo, Sheng Zhi-Yong, Xia Zhao-Fan
Chinese PLA Institute of Burn Surgery & Burn Center, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Biochem Biophys Res Commun. 2009 Jul 31;385(3):418-23. doi: 10.1016/j.bbrc.2009.05.081. Epub 2009 May 22.
Angiotensin II is critically involved in skin wound healing, but the underlying mechanism remains unclear. This study investigated the effect of angiotensin II on type I collagen gene activation in human dermal fibroblasts and the possible mechanism involved. Angiotensin II stimulated the mRNA and protein expression of type I collagen and TGF-beta1. Effects were abolished by the angiotensin AT1 receptor antagonist ZD7155 but not by the AT2 blocker PD123319. Blockade of TGF-beta1 markedly inhibited angiotensin II-induced type I collagen gene expression. Activator protein-1 (AP-1) decoy ODNs transfection suppressed angiotensin II-induced TGF-beta1 expression, and also, diminished type I collagen expression. These data indicated that angiotensin II induces collagen gene activation in human dermal fibroblasts through an AT1-mediated AP-1/TGF-beta1 signaling pathway.
血管紧张素II在皮肤伤口愈合中起关键作用,但其潜在机制仍不清楚。本研究调查了血管紧张素II对人真皮成纤维细胞I型胶原基因激活的影响及可能涉及的机制。血管紧张素II刺激了I型胶原和转化生长因子β1(TGF-β1)的mRNA及蛋白表达。血管紧张素AT1受体拮抗剂ZD7155可消除这些作用,但AT2受体阻滞剂PD123319则不能。阻断TGF-β1可显著抑制血管紧张素II诱导的I型胶原基因表达。激活蛋白-1(AP-1)诱饵寡核苷酸转染可抑制血管紧张素II诱导的TGF-β1表达,同时也减少了I型胶原的表达。这些数据表明,血管紧张素II通过AT1介导的AP-1/TGF-β1信号通路诱导人真皮成纤维细胞中的胶原基因激活。