Enhanced angiotensin-converting enzyme 2 attenuates angiotensin II-induced collagen production via AT1 receptor-phosphoinositide 3-kinase-Akt pathway

被引：11

作者：

Bu, Le ^{[1
,2
]}

Qu, Shen ^{[2
]}

Gao, Xiang ^{[3
]}

Zou, J. -J. ^{[1
]}

Tang, Wei ^{[1
]}

Sun, L. -L. ^{[1
]}

Liu, Z. -M. ^{[1
]}

机构：

[1] Second Mil Med Univ, Changzheng Hosp, Dept Endocrinol, Shanghai 200003, Peoples R China

[2] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Endocrinol, Shanghai 200072, Peoples R China

[3] Second Mil Med Univ, Changzheng Hosp, Dept Nephrol, Shanghai 200003, Peoples R China

来源：

ENDOCRINE | 2011年 / 39卷 / 02期

关键词：

Angiotensin-converting enzyme 2 (ACE2); Angiotensin II; Phosphoinositide; 3-kinase; Akt; Collagen synthesis; GROWTH-FACTOR-BETA; CELL-PROLIFERATION; MESANGIAL CELLS; SKIN FIBROSIS; ACTIVATION; EXPRESSION; SYSTEM; KINASE; INHIBITION; INDUCTION;

D O I：

10.1007/s12020-010-9435-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recent reports support a protective role for angiotensin-converting enzyme 2 (ACE2) against glomerular diseases, especially by decreasing of extracellular matrix (ECM) proteins. However, the mechanism regulating this effect appears to be complex and poorly understood. Our aim was to investigate whether or not ACE2 amelioratesthe profibrotic effects of Ang II-mediated, Akt-dependent pathways in the mouse mesangial cell line, MES-13.Gene transfer of ACE2 suppressed Ang II-activated Akt-phosphorylation, accompanied by a decreased level of collagen type I in cells. In addition, Ang II-induced collagen type I synthesis in MES-13s by activating the Ang II/AT-1R-PI3K pathway. This transactivation was dependent on cAMP/Epac but not on PKA. TGF-beta RI played a pivotal role in this signaling pathway inducing collagen deposition effects which could be reversed by ACE2 gene transfer in MES-13 cells. The results revealed that gene transfer of ACE2 regulated Ang II-mediated AT1R-TGF beta RI-PI3K-Akt signaling and involved the synthesis of collagen. The beneficial effect of ACE2 overexpression appeared to result mainly from blocking phosphorylation of Akt in mesangial cells, suggesting that the ACE2 gene might be a novel therapeutic target for glomerular diseases.

引用

页码：139 / 147

页数：9

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