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整合素α5β1表达下调参与人急性A型主动脉夹层形成
薛明明, 杨依霖, 邢玲玉, 徐斐翔, 汪升, 陈玉梅, 陈斌, 宋振举, 姚晨玲, 顾国嵘, 童朝阳
复旦大学附属中山医院急诊科, 上海 200032
摘要:
目的 探讨整合素α5β1在急性A型主动脉夹层(acute type A aortic dissection, AAAD)患者病变组织及人主动脉平滑肌细胞(human aortic smooth muscle cell, HASMC)中的表达情况及可能的调控机制。方法 免疫组织化学检测AAAD患者病变组织整合素α5β1、磷酸化黏着斑激酶(phosphorylated focal adhesion kinase, p-FAK)和Caspase 3的蛋白表达水平。免疫荧光检测HASMC中整合素α5β1、p-FAK的表达。siRNA下调HASMC中整合素α5β1的表达水平,CCK-8实验检测HASMC的增殖活力,流式细胞仪检测HASMC细胞凋亡。结果 免疫组化检测结果显示,与正常组织相比,AAAD患者病变组织整合素α5β1表达下降(P<0.05)。免疫荧光检测结果显示,正常HASMC中,整合素α5β1和FAK定位于相同部位。转染siRNA下调整合素α5β1的表达后,HASMC增殖减少、凋亡增加(P<0.001),整合素α5β1及p-FAK蛋白的表达下调(P<0.001)。结论 AAAD患者病变组织整合素 α5β1/FAK信号通路表达抑制;体外抑制该信号通路可导致HASMC细胞增殖减少、凋亡增加。
关键词:  整合素α5β1  急性A型主动脉夹层  主动脉平滑肌细胞
DOI:10.12025/j.issn.1008-6358.2023.20221872
分类号:
基金项目:上海市科学技术委员会基金(21Y11902200),上海市卫生健康委员会基金(201940163).
Down-regulation of integrin α5β1 participates in the formation of acute type A aortic dissection in human
XUE Ming-ming, YANG Yi-lin, XING Ling-yu, XU Fei-xiang, WANG Sheng, CHEN Yu-mei, CHEN Bin, SONG Zhen-ju, YAO Chen-ling, GU Guo-rong, TONG Chao-yang
Department of Emergency, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Abstract:
Objective To explore expression levels of integrin α5β1 in lesion tissues of patients with acute type A aortic dissection (AAAD) and human aortic smooth muscle cells (HASMC) and the possible regulatory mechanism. Methods Immunohistochemistry was used to detect expression levels of integrin α5β1, phosphorylated focal adhesion kinase (p-FAK) and Caspase 3 proteins in the lesion tissues of AAAD patients. Immunofluorescence was used to detect integrins α5β1 and p-FAK expressions in HASMC. siRNA was used to downregulate integrin α5β1 in HASMC, CCK-8 and flow cytometry were used to detect the proliferation activity and apoptosis of HASMC, respectively. Results The expression of integrin α5β1 at lesion tissues in AAAD patients was decreased (P<0.05). Integrins α5β1 and FAK expressed in the same sites of normal HASMC. After down regulating expression of integrin α5β1 in HASMC, the smooth muscle cells showed decreased proliferation and increased apoptosis (P<0.001). The expression of α5β1 and FAK proteins was downregulated (P<0.001). Conclusions Integrin α5β1/FAK signal pathway in the aorta of AAAD patients is down regulated, and the HASMC proliferation decreases and apoptosis increases after this signal pathway is inhibited.
Key words:  integrin α5β1  acute type A aortic dissection  aortic smooth muscle cell
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