Serpine1 Regulates the Enhanced Inhibitory Effect of CHIR99021 Combined with Fibroblast Growth Factor 2 on Myocardial Fibrosis After Myocardial Infarction in Mice.

Yangyang Jia, Xiangqin Tian, Mengyu Wei, Pingping Xu, Jikui Wang, Yaping Xu, Changye Sun, Zhikun Guo

Abstract read

In one paragraph

Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

Naringin Attenuates Steatosis, Oxidative Stress, Inflammation, and Fibrosis in MASH: Network Pharmacology and In Vivo Study.Biomolecules · 2026
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5 · Who and what money

Authors and funding

8 authors.

Yangyang JiaHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.ORCID 0000-0003-3380-4016

Xiangqin TianHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.

Mengyu WeiHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.

Pingping XuHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.

Jikui WangHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.

Yaping XuHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.

Changye SunHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.

Zhikun GuoHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.

Funding

Key Scientific Research Project of Higher Education Institutions in Henan Province 26A310004National Natural Science Foundation of China 81570268National Natural Science Foundation of China 82170237Scientific and Technological Project of Henan Province 242102310413

6 · The paper itself

Abstract

Cardiac fibrosis is a pathological phenomenon caused by tissue remodeling and excessive matrix proliferation under stress conditions. CHIR99021 is a selective glycogen synthase kinase-3 inhibitor that has shown potential in cardiovascular regeneration therapy. Fibroblast growth factor 2 (FGF2) has a protective effect on ischemic myocardium. However, the effect and underlying mechanism of the combined use of CHIR99021 and FGF2 on myocardial fibrosis remains unclear. In this study, we found that the combination of CHIR99021 and FGF2 could significantly inhibit the activation of cardiac fibroblasts (CFs) and alleviate the formation of collagen scars in mouse myocardium. By analyzing the expression levels of fibrotic proteins, such as ColI, ColIII and alpha smooth muscle actin (α-SMA) in fibroblasts in vitro and in vivo, we confirmed the inhibitory effect of CHIR99021 combined with FGF2 on the activation of fibroblasts. Transcriptome sequencing showed that CHIR99021 and FGF2 inhibited the expression level of Serpine1 through the transforming growth factor-β (TGF-β) and Focal Adhesion Kinase (FAK) signaling pathways. By analyzing the regulatory effect of overexpressed and knocked-down Serpine1 on fibrotic pathway-related proteins in CFs, we verified that Serpine1 is a key target for inhibiting fibrosis. In conclusion, this study provides evidence that Serpine1 may be a potential mechanism that enables CHIR99021 combined with FGF2 to improve myocardial fibrosis.

Indexed as

Fibroblast Growth Factor 2Myocardial InfarctionMyocardiumPlasminogen Activator Inhibitor 1PyridinesPyrimidinesAnimalsFibroblastsFibrosisMaleMiceMice, Inbred C57BLSignal TransductionTransforming Growth Factor betaChir 99021Fibroblast Growth Factor 2Plasminogen Activator Inhibitor 1PyridinesPyrimidinesTransforming Growth Factor betacardiac fibroblastscardiac fibrosisCHIR99021FGF2Serpine1

Identifiers

PMID41751765

DOI10.3390/ijms27041627

PMCPMC12940905

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.