Role of TGF-β1/Smad signaling in angiotensinⅡmediated down-regula-tion of connexin 43
10.3969/j.issn.1000-4718.2016.10.001
- VernacularTitle:TGF-β1／Smad通路在血管紧张素Ⅱ下调缝隙连接蛋白43表达中的作用
- Author:
Jingying HOU
;
Changqing ZHOU
;
Shaoxin ZHENG
;
Tianzhu GUO
;
Huibao LONG
;
Quanhua WU
;
Tingting ZHONG
;
Tong WANG
- Publication Type:Journal Article
- Keywords:
Angiotensin Ⅱ;
Connexin 43;
Transforming growth factor-β1;
Smad;
Myocardial infarction
- From:
Chinese Journal of Pathophysiology
2016;32(10):1729-1736
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To analyze the alterations of angiotensin Ⅱ (Ang Ⅱ), connexin 43 (Cx43), angiotenisinⅡreceptor type 1 (AT1) and signaling molecules in the TGF-β1/Smad pathway in different regions of the left ventricular heart tissue for exploring whether Ang Ⅱregulates Cx43 expression via the TGF-β1/Smad signaling pathway in myocardial infarction ( MI) rats.METHODS:MI was induced in 20 male Sprague-Dawley rats by the left anterior descending coronary artery ligation.The rats were then randomized into 2 groups.In the losartan group, 20 mg· kg-1· d-1 of losartan were ad-ministered for 2 weeks.Heart functions were assessed after surgery and 2 weeks later again following the above treatments . All the rats were sacrificed and relevant molecules , including Ang Ⅱ, AT1, and Cx43 were determined thereafter in diffe-rent areas of the left ventricle .TGF-β1 and its downstream signaling molecules , including Smad 2, Smad 3 and Smad 7, were also detected .RESULTS:In losartan group , both left ventricular internal dimension diastole ( LVIDd) and left ven-tricular internal dimension systole (LVIDs) were smaller, with diminished interventricular septal thickness (IVSd) and left ventricular posterior wall depth ( LVPWd ) and distinct improvement of left ventricular ejection fraction ( LVEF ) ( P<0.05 ) .Losartan therapy exhibited a reduction of Ang Ⅱin the infarct zone and the border zone in the cardiac tissues .AT1 was obviously attenuated in the infarct zone with an enhanced expression of Cx 43, which was also elevated in the border zone and none infarct zone .TGF-β1, Smad 2 and Smad 3 were decreased in different zones of the left ventricle , while Smad 7, in contrary to the above factors , presented a converse alteration .CONCLUSION:The activation of Ang Ⅱpro-vokes downregulation of Cx 43 through TGF-β1/Smad signaling pathway in MI rats .
