{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang D"],"funding":["National Natural Science Foundation of China","Henan Provincial Science and Technology Research Project"],"pagination":["103887"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12628024"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["87"],"pubmed_abstract":["<h4>Backgrounds</h4>Cardiac remodeling, mediated by fibroblast-to-myofibroblast differentiation, is a key pathophysiologic step to determine the prognosis of patients following myocardial infarction (MI). Paired-related homeobox 1 (Prrx1) is a master transcription factor of fibroblasts for myofibroblastic lineage progression. Protein S-nitrosylation by nitric oxide (NO) is highly related to regulate cellular functions. This study is to investigate whether and how Prrx1 S-nitrosylation plays a key role in postischemic remodeling of heart.<h4>Methods</h4>The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac fibrosis was assessed using Masson staining. Heart function was measured by echocardiography.<h4>Results</h4>MI induced cardiac remodeling as cardiac fibrosis and heart dysfunction in mice, accompanied with increased Prrx1 transcriptional activity, but inhibited by N-acetyl-cysteine administration. In recombinant human protein, NO donors increased Prrx1 S-nitrosylation at cysteine 207 (C207). In human cardiac fibroblasts, oxygen-glucose deprivation or transforming growth factor beta upregulated NO productions, Prrx1 S-nitrosylation, Prrx1 transcriptional activity, Wnt5a gene expression, and fibroblast-to-myofibroblast differentiation, which were abolished by Prrx1-C207R mutant. In vivo, exogenous expression of Prrx1-C209R alleviated MI-induced cardiac fibrosis and promoted the recovery of heart functions in mice. Fibroblast-specific Prrx1 gene knockout prevented cardiac fibrosis and heart dysfunctions in mice fowling MI. In human patients with post-MI, Prrx1 S-nitrosylation was increased.<h4>Conclusion</h4>Upregulation of Prrx1 by S-nitrosylation increases Wnt5a gene expression to induce fibroblast-to-myofibroblast differentiation, which contributes to cardiac remodeling after MI. In perspective, targeting Prrx1 S-nitrosylation should be considered to improve the outcome of patients with MI."],"journal":["Redox biology"],"pubmed_title":["S-nitrosylation of paired-related homeobox 1 promotes cardiac remodeling following myocardial infarction."],"pmcid":["PMC12628024"],"funding_grant_id":["242102310156","81500260"],"pubmed_authors":["Liu H","Huang C","Zhou S","Huang G","Wang S","Wang D","Liang Z","Tang Y","Yu X"],"additional_accession":[]},"is_claimable":false,"name":"S-nitrosylation of paired-related homeobox 1 promotes cardiac remodeling following myocardial infarction.","description":"<h4>Backgrounds</h4>Cardiac remodeling, mediated by fibroblast-to-myofibroblast differentiation, is a key pathophysiologic step to determine the prognosis of patients following myocardial infarction (MI). Paired-related homeobox 1 (Prrx1) is a master transcription factor of fibroblasts for myofibroblastic lineage progression. Protein S-nitrosylation by nitric oxide (NO) is highly related to regulate cellular functions. This study is to investigate whether and how Prrx1 S-nitrosylation plays a key role in postischemic remodeling of heart.<h4>Methods</h4>The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac fibrosis was assessed using Masson staining. Heart function was measured by echocardiography.<h4>Results</h4>MI induced cardiac remodeling as cardiac fibrosis and heart dysfunction in mice, accompanied with increased Prrx1 transcriptional activity, but inhibited by N-acetyl-cysteine administration. In recombinant human protein, NO donors increased Prrx1 S-nitrosylation at cysteine 207 (C207). In human cardiac fibroblasts, oxygen-glucose deprivation or transforming growth factor beta upregulated NO productions, Prrx1 S-nitrosylation, Prrx1 transcriptional activity, Wnt5a gene expression, and fibroblast-to-myofibroblast differentiation, which were abolished by Prrx1-C207R mutant. In vivo, exogenous expression of Prrx1-C209R alleviated MI-induced cardiac fibrosis and promoted the recovery of heart functions in mice. Fibroblast-specific Prrx1 gene knockout prevented cardiac fibrosis and heart dysfunctions in mice fowling MI. In human patients with post-MI, Prrx1 S-nitrosylation was increased.<h4>Conclusion</h4>Upregulation of Prrx1 by S-nitrosylation increases Wnt5a gene expression to induce fibroblast-to-myofibroblast differentiation, which contributes to cardiac remodeling after MI. In perspective, targeting Prrx1 S-nitrosylation should be considered to improve the outcome of patients with MI.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T17:35:18.166Z","creation":"2026-05-19T03:12:01.657Z"},"accession":"S-EPMC12628024","cross_references":{"pubmed":["41168006"],"doi":["10.1016/j.redox.2025.103887"]}}