Dataset Information

Puerarin Protects against Cardiac Fibrosis Associated with the Inhibition of TGF-?1/Smad2-Mediated Endothelial-to-Mesenchymal Transition.

ABSTRACT: BACKGROUND:Puerarin is a kind of flavonoids and is extracted from Chinese herb Kudzu root. Puerarin is widely used as an adjuvant therapy in Chinese clinics. But little is known about its effects on regulating cardiac fibrosis. METHODS:Mice were subjected to transverse aorta constriction (TAC) for 8 weeks; meanwhile puerarin was given 1 week after TAC. Cardiac fibrosis was assessed by pathological staining. The mRNA and protein changes of CD31 and vimentin in both animal and human umbilical vein endothelial cells (HUVECs) models were detected. Immunofluorescence colocalization of CD31 and vimentin and scratch test were carried out to examine TGF-?1-induced changes in HUVECs. The agonist and antagonist of peroxisome proliferator-activated receptor-? (PPAR-?) were used to explore the underlying mechanism. RESULTS:Puerarin mitigated TAC-induced cardiac fibrosis, accompanied with suppressed endothelial-to-mesenchymal transition (EndMT). The consistent results were achieved in HUVECs model. TGF-?1/Smad2 signaling pathway was blunted and PPAR-? expression was upregulated in puerarin-treated mice and HUVECs. Pioglitazone could reproduce the protective effect in HUVECs, while GW9662 reversed this effect imposed by puerarin. CONCLUSION:Puerarin protected against TAC-induced cardiac fibrosis, and this protective effect may be attributed to the upregulation of PPAR-? and the inhibition of TGF-?1/Smad2-mediated EndMT.

SUBMITTER: Jin YG

PROVIDER: S-EPMC5468594 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Puerarin Protects against Cardiac Fibrosis Associated with the Inhibition of TGF-<i>β</i>1/Smad2-Mediated Endothelial-to-Mesenchymal Transition.

Jin Ya-Ge YG Yuan Yuan Y Wu Qing-Qing QQ Zhang Ning N Fan Di D Che Yan Y Wang Zhao-Peng ZP Xiao Yang Y Wang Sha-Sha SS Tang Qi-Zhu QZ

PPAR research 20170530

<h4>Background</h4>Puerarin is a kind of flavonoids and is extracted from Chinese herb Kudzu root. Puerarin is widely used as an adjuvant therapy in Chinese clinics. But little is known about its effects on regulating cardiac fibrosis.<h4>Methods</h4>Mice were subjected to transverse aorta constriction (TAC) for 8 weeks; meanwhile puerarin was given 1 week after TAC. Cardiac fibrosis was assessed by pathological staining. The mRNA and protein changes of CD31 and vimentin in both animal and human ...[more]

PMID: 28638404

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Project description:Rationale: Cardiac fibrosis is an integral constituent of every form of chronic heart disease, and persistence of fibrosis reduces tissue compliance and accelerates the progression to heart failure. Relaxin-2 is a human hormone, which has various physiological functions such as mediating renal vasodilation in pregnancy. Its recombinant form Serelaxin has recently been tested in clinical trials as a therapy for acute heart failure but did not meet its primary endpoints. The aim of this study is to examine whether Serelaxin has an anti-fibrotic effect in the heart and therefore could be beneficial in chronic heart failure. Methods: We utilized two different cardiac fibrosis mouse models (ascending aortic constriction (AAC) and Angiotensin II (ATII) administration via osmotic minipumps) to assess the anti-fibrotic potential of Serelaxin. Histological analysis, immunofluorescence staining and molecular analysis were performed to assess the fibrosis level and indicate endothelial cells which are undergoing EndMT. In vitro TGF?1-induced endothelial-to-mesenchymal transition (EndMT) assays were performed in human coronary artery endothelial cells and mouse cardiac endothelial cells (MCECs) and were examined using molecular methods. Chromatin immunoprecipitation-qPCR assay was utilized to identify the Serelaxin effect on chromatin remodeling in the Rxfp1 promoter region in MCECs. Results: Our results demonstrate a significant and dose-dependent anti-fibrotic effect of Serelaxin in the heart in both models. We further show that Serelaxin mediates this effect, at least in part, through inhibition of EndMT through the endothelial Relaxin family peptide receptor 1 (RXFP1). We further demonstrate that Serelaxin administration is able to increase its own receptor expression (RXFP1) through epigenetic regulation in form of histone modifications by attenuating TGF?-pSMAD2/3 signaling in endothelial cells. Conclusions: This study is the first to identify that Serelaxin increases the expression of its own receptor RXFP1 and that this mediates the inhibition of EndMT and cardiac fibrosis, suggesting that Serelaxin may have a beneficial effect as anti-fibrotic therapy in chronic heart failure.

Dataset Information

Puerarin Protects against Cardiac Fibrosis Associated with the Inhibition of TGF-?1/Smad2-Mediated Endothelial-to-Mesenchymal Transition.

Publications

Puerarin Protects against Cardiac Fibrosis Associated with the Inhibition of TGF-<i>β</i>1/Smad2-Mediated Endothelial-to-Mesenchymal Transition.

Similar Datasets

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