Ursodeoxycholic acid inhibits intimal hyperplasia, vascular smooth muscle cell excessive proliferation, migration via blocking miR-21/PTEN/AKT/mTOR signaling pathway
Authors: Yongzhi Jin
Yi Huang
Mengfan Li
Guang Zeng
Rong Huang
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Atherosclerosis; intimal hyperplasia; miR-21/PTEN/AKT/mTOR signaling pathway; proliferation; vascular smooth muscle cell.
Affiliations: Department of General Surgery, Putuo Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract:  Excessive migration and proliferation of vascular smooth muscle cells (VSMCs) are critical cellular events that lead to intimal hyperplasia in atherosclerosis and restenosis. In this study, we investigated the protective effects of ursodeoxycholic acid (UDCA) on intimal hyperplasia and VSMC proliferation and migration, and the underlying mechanisms by which these events occur. A rat unilateral carotid artery was ligated to induce vascular injury and the microRNA (miRNA) expression profiles were determined using miRNA microarray analysis. We observed that UDCA significantly reduced the degree of intimal hyperplasia and induced miR-21 dysregulation. Restoration of miR-21 by agomir-miR-21 reversed the protective effects of UDCA on intimal hyperplasia and proliferation in vivo. In vitro, UDCA suppressed PDGF-BB-induced VSMC proliferation, invasion and migration in a dose-dependent manner, whereas the suppressive effect of UDCA was abrogated by overexpression of miR-21 in PDGF-BB-incubated VSMCs. Furthermore, we identified that miR-21 in VSMCs targeted the phosphatase and tensin homolog (PTEN), a tumor suppressor gene, negatively modulated the AKT/mTOR pathway. More importantly, we observed that that UDCA suppressed AKT/mTOR signaling pathway in the carotid artery injury model, whereas this pathway was reactivated by overexpression of miR-21. Taken together, our findings indicated that UDCA inhibited intimal hyperplasia and VSMCs excessive migration and proliferation via blocking miR-21/PTEN/AKT/mTOR signaling pathway, which suggests that UDCA may be a promising candidate for the therapy of atherosclerosis. 

Retracted: No

PubPeer comments:
 Expression of Concern, [17 March 2022] --------------------- We, the Publisher and Editor of Cell Cycle are issuing an Expression of Concern for the following article: Rong Huang, Yi Huang, Guang Zeng, Mengfan Li, and Yongzhi Jin. Ursodeoxycholic acid inhibits intimal hyperplasia, vascular smooth muscle cell excessive proliferation, migration via blocking miR-21 PTEN AKT mTOR signaling pathway. Cell Cycle. 2020;19(8): 918-932. doi: 10.1080 15384101.2020.1732514. After publication of this article, questions about the scientific integrity of the article content were brought to the Publisher and Editoru2019s attention. We have reached out to the authors requesting that they supply information that would confirm the articleu2019s integrity, but the authors have not responded to our queries within the requested timeframe. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. ,