The inhibition of FTO attenuates the antifibrotic effect of leonurine in rat cardiac fibroblasts

作者全名："Meng, Yuwei; Xi, Tianlan; Fan, Jun; Yang, Qiyu; Ouyang, Jing; Yang, Jiadan"

作者地址："[Meng, Yuwei; Xi, Tianlan; Yang, Jiadan] Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing, Peoples R China; [Meng, Yuwei; Xi, Tianlan] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Fan, Jun] Third Mil Med Univ, Army Med Univ, Daping Hosp, Dept Breast & Thyroid Surg, Chongqing 400042, Peoples R China; [Yang, Qiyu] Chongqing Univ, Canc Hosp, Dept Radiat Oncol, Chongqing, Peoples R China; [Yang, Qiyu] Chongqing Canc Inst, Chongqing, Peoples R China; [Yang, Qiyu] Chongqing Canc Hosp, Chongqing, Peoples R China; [Ouyang, Jing] Chongqing Publ Hlth Med Ctr, Clin Res 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)，Chongqing Publ Hlth Med Ctr, Clin Res Ctr, Chongqing, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001147010400001

JCR分区：Q2

影响因子：3.1

年份：2024

卷号：693

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Leonurine; FTO; Myocardial fibrosis

摘要："Background: Myocardial fibrosis (MF) is a common pathological condition in cardiovascular diseases that often causes severe cardiac dysfunction. MF is characterized by changes in cardiomyocytes, cardiac fibroblasts (CFs), levels of collagen (Col) -1, -3, and overdeposition of the extracellular matrix. Our previous research showed that leonurine (LE) effectively inhibits collagen synthesis and differentiation of CFs, but the mechanism is not fully elucidated. Recent evidence indicates that fat mass and obesity-associated proteins (FTO) regulates the occurrence and development of MF. This study aimed to explore the role of FTO in the antifibrotic effects of LE. Methods: Neonatal rat CFs were isolated, and induced using angiotensin II (Ang II) to establish a cell model of MF. Cell viability, wound healing and transwell assays were used to detect cell activity and migration ability. The protein and mRNA levels of MF-related factors were measured following stimulation with Ang II and LE under normal conditions or after FTO knockdown. The RNA methylation level was measured by dot blot assay. Results: The results showed that LE (20, 40 mu M) was not toxic to normal CFs. LE reduced the proliferation, migration and collagen synthesis of Ang II-induced CFs. Further investigation showed that FTO was downregulated by Ang II stimulation, whereas LE reversed this effect. FTO knockdown facilitated the migration of CFs, upregulated the protein levels of Col-3, alpha-SMA and Col-1 in Ang II and LE-stimulated CFs, and enhanced the fluorescence intensity of alpha-SMA. Furthermore, LE reduced N6-methyladenosine (m6A) RNA methylation, which was partially blocked by FTO knockdown. FTO knockdown also reduced the expression levels of p53 protein in Ang II and LE-stimulated CFs. Conclusions: Our findings suggest that the inhibition of FTO may attenuate the antifibrotic effect of LE in CFs, suggesting that FTO may serve as a key protein for anti-MF of LE."

基金机构："National Natural Science Foundation of China, China [81603330]; Natural Science Foundation of Chongqing, China [CSTB2023NSCQ-MSX0392]; Chongqing Science and Technology Bureau Research project, China [CSTB2022BSXM-JCX0081]"

基金资助正文："<BOLD>Funding</BOLD> This work was supported by the National Natural Science Foundation of China, China (No.81603330) , Natural Science Foundation of Chongqing, China (No. CSTB2023NSCQ-MSX0392) and Chongqing Science and Technology Bureau Research project, China (No. CSTB2022BSXM-JCX0081) ."