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在糖尿病条件下，阿卡波糖通过靶向血管平滑肌细胞中的微小RNA-143来减弱其迁移/增殖。

Acarbose attenuates migration/proliferation via targeting microRNA-143 in vascular smooth muscle cells under diabetic conditions.

作者信息

Chuang Wei-Yuan, Yu Meng-Hsun, Yang Tsung-Yuan, Chan Kuei-Chuan, Wang Chau-Jong

机构信息

Department of Internal Medicine, Chung-Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.

School of Medicine, Institute of Medicine, Chung-Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.

出版信息

J Food Drug Anal. 2020 Sep 15;28(3):461-474. doi: 10.38212/2224-6614.1241.

DOI:10.38212/2224-6614.1241
PMID:35696095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9261793/
Abstract

Acarbose (an α-glucosidase inhibitor) has been demonstrated to reduce the progression of atherosclerosis without affecting serum levels of glucose in rabbits fed a high cholesterol diet. The main focus of recent atherosclerosis studies has been microRNA targets. However, the mechanism by which acarbose targets miRNA-mediated atherosclerosis remains unclear. This study aimed to evaluate the effect of acarbose on microRNA-related regulation of rat aortic vascular smooth cell line (A7r5 cell) migration and proliferation induced by diabetic conditions. We reported that acabose exhibit significantly inhibits proliferative and cell migration abilities in A7r5 cells. The expression of protein and levels of mRNA were measured by Western blot analysis and real-time PCR. Acarbose inhibited the phosphorylation of focal adhesion kinase (FAK) and phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt), Ras signals, small GTPase proteins expression to attenuate cell migration and proliferation. Furthermore, acarbose upregulated the expression of miR-143, and transfected miR-143 mimic and its inhibitor to explore its mechanism. In conclusion, acarbose reduces VSMC migration and proliferation via upregulating miR-143 to inhibit Ras-related signaling, and potentially prevention of atherosclerosis.

摘要

阿卡波糖（一种α-葡萄糖苷酶抑制剂）已被证明在喂食高胆固醇饮食的兔子中可降低动脉粥样硬化的进展，而不影响血清葡萄糖水平。近期动脉粥样硬化研究的主要焦点是微小RNA靶点。然而，阿卡波糖靶向微小RNA介导的动脉粥样硬化的机制仍不清楚。本研究旨在评估阿卡波糖对糖尿病条件诱导的大鼠主动脉血管平滑肌细胞系（A7r5细胞）迁移和增殖的微小RNA相关调节的影响。我们报道阿卡波糖在A7r5细胞中显著抑制增殖和细胞迁移能力。通过蛋白质印迹分析和实时PCR测量蛋白质表达和mRNA水平。阿卡波糖抑制粘着斑激酶（FAK）和磷酸肌醇3激酶（PI3K）/蛋白激酶B（Akt）的磷酸化、Ras信号、小GTPase蛋白表达，以减弱细胞迁移和增殖。此外，阿卡波糖上调miR-143的表达，并转染miR-143模拟物及其抑制剂以探索其机制。总之，阿卡波糖通过上调miR-143抑制Ras相关信号传导来减少血管平滑肌细胞迁移和增殖，并可能预防动脉粥样硬化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/f153646fad27/jfda-28-03-461f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/5742dce3d170/jfda-28-03-461f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/62b89277e431/jfda-28-03-461f2a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/40a54c79b334/jfda-28-03-461f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/5fcb66d5092a/jfda-28-03-461f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/a93b539c0bad/jfda-28-03-461f5a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/f153646fad27/jfda-28-03-461f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/5742dce3d170/jfda-28-03-461f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/62b89277e431/jfda-28-03-461f2a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/40a54c79b334/jfda-28-03-461f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/5fcb66d5092a/jfda-28-03-461f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/a93b539c0bad/jfda-28-03-461f5a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa1/9261793/f153646fad27/jfda-28-03-461f6.jpg

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