The p53/miR-29a-3p axis mediates the antifibrotic effect of leonurine on angiotensin II-stimulated rat cardiac fibroblasts

作者全名："Xi, Tianlan; Wang, Ruiyu; Pi, Damao; Ouyang, Jing; Yang, Jiadan"

作者地址："[Xi, Tianlan; Pi, Damao; Yang, Jiadan] Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing, Peoples R China; [Xi, Tianlan; Wang, Ruiyu] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Ouyang, Jing] Clin Res Ctr, Chongqing Publ Hlth Med Ctr, Chongqing, Peoples R China"

通信作者："Yang, JD (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing, Peoples R China.; Ouyang, J (通讯作者)，Clin Res Ctr, Chongqing Publ Hlth Med Ctr, Chongqing, Peoples R China."

来源：EXPERIMENTAL CELL RESEARCH

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000960384300001

JCR分区：Q2

影响因子：3.3

年份：2023

卷号：426

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Leonurine; p53; Myocardial fibrosis; miR-29a-3p; Cardiac fibroblasts; Rats

摘要："Overactivation of cardiac fibroblasts (CFs) is one of the main causes of myocardial fibrosis (MF), and inhibition of CF activation is a crucial strategy for MF therapy. A previous study by our group demonstrated that leonurine (LE) effectively inhibits collagen synthesis and myofibroblast generation originated from CFs, and eventually mitigates the progression of MF (where miR-29a-3p is likely to be a vital mediator). However, the underlying mechanisms involved in this process remain unknown. Thus, the present study aimed to investigate the precise role of miR-29a-3p in LE-treated CFs, and to elucidate the pharmacological effects of LE on MF. Neonatal rat CFs were isolated and stimulated by angiotensin II (Ang II) to mimic the pathological process of MF in vitro. The results show that LE distinctly inhibits collagen synthesis, as well as the proliferation, differentiation and migration of CFs, all of which could be induced by Ang II. In addition, LE promotes apoptosis in CFs under Ang II stimulation. During this process, the down-regulated expressions of miR-29a-3p and p53 are partly restored by LE. Either knockdown of miR-29a-3p or inhibition of p53 by PFT-alpha (a p53 inhibitor) blocks the antifibrotic effect of LE. Notably, PFT-alpha suppresses miR-29a-3p levels in CFs under both normal and Ang II-treated conditions. Furthermore, ChIP analysis confirmed that p53 is bound to the promoter region of miR-29a-3p, and directly regulates its expression. Overall, our study demonstrates that LE upregulates p53 and miR-29a-3p expression, and subsequently inhibits CF overactivation, suggesting that the p53/miR-29a-3p axis may play a crucial role in mediating the antifibrotic effect of LE against MF."

基金机构："Natural Science Foundation of Sichuan Province,China [2022NSFSC1570]; National Natural Science Foundation of China,China [81603330]; Chongqing Traditional Chinese Medicine Science and Technology Project, China [ZY201802043]; Chongqing Science and Technology Bureau Research project ,China [CSTB2022BSXMJCX0081]"

基金资助正文："This work was supported by the Natural Science Foundation of Sichuan Province,China (No.2022NSFSC1570); the National Natural Science Foundation of China,China (No.81603330); Chongqing Traditional Chinese Medicine Science and Technology Project, China (No. ZY201802043); Chongqing Science and Technology Bureau Research project ,China (No.CSTB2022BSXMJCX0081)."