標題: Angiotensin II downregulates ACE2-mediated enhancement of MMP-2 activity in human cardiofibroblasts
作者: Kuan, Tang-Ching
Chen, Mu-Yuan
Liao, Yan-Chiou
Ko, Li
Hong, Yi-Han
Yen, Chun-Yi
Hsieh, Wen-Yeh
Cheng, Kun-Shan
Wu, Chien-Liang
Lin, Chih-Sheng
生物科技學系
Department of Biological Science and Technology
關鍵字: angiotensin II;angiotensin-converting enzyme II;matrix metalloproteinases-2;human cardiofibroblasts
公開日期: 1-十二月-2013
摘要: Angiotensin converting enzyme II (ACE2) is a component of the renin-angiotensin system (RAS) that negatively regulates angiotensin II (Ang II). Ang II, in turn, affects the expression of matrix metalloproteinases (MMPs) to induce heart remodeling. The specific mechanisms by which ACE2 regulates MMP-2, however, remain unclear. The aim of this study was to investigate the regulatory relationships between Ang II, ACE2, and MMP-2. ACE2 expression was upregulated and downregulated in human cardiofibroblasts (HCFs) by lentiviral infection. Effects on MMP-2 activity, shed ACE2 activity, extracellular signal-regulated kinase (ERK) signaling pathway, and ADAM metallopeptidase domain 17 (ADAM17) expression were assessed. ACE2 increased MMP-2 activity, and Ang II inhibited this effect through the Ang II type-1 receptor (AT1R) and ERK1/2 signaling pathway. Ang II also reduced the effect of ACE2 on ERK1/2 levels, the activity of shed ACE2, and adam17 expression in HCFs. Additionally, these Ang II-mediated reductions could be attenuated by AT1R antagonist valsartan. In conclusion, these data help to clarify how ACE2 and Ang II interact to regulate MMP-2 and control tissue remodeling in heart disease.
URI: http://dx.doi.org/10.1139/bcb-2013-0031
http://hdl.handle.net/11536/23238
ISSN: 0829-8211
DOI: 10.1139/bcb-2013-0031
期刊: BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
Volume: 91
Issue: 6
起始頁: 435
結束頁: 442
顯示於類別:期刊論文


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