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The aim of this study is to investigate whether the transcriptional factor paired\u2010related homeobox 2 (Prrx2) regulates Wnt5a gene expression and the role in myocardial fibrosis following MI. The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodelling was assessed by measuring interstitial fibrosis performed with Masson staining. Cell differentiation was examined by analysis the expression of alpha\u2010smooth muscle actin (\u03b1\u2010SMA). Both Prrx2 and Wnt5a gene expressions were up\u2010regulated in mice following MI, accompanied with increased mRNA and protein levels of \u03b1\u2010SMA, collagen I and collagen III, compared to mice with sham surgery. Adenovirus\u2010mediated gene knock down of Prrx2 increased survival rate, alleviated cardiac fibrosis, decreased infarction sizes and improved cardiac functions in mice with MI. Importantly, inhibition of Prrx2 suppressed ischaemia\u2010induced Wnt5a gene expression and Wnt5a signalling. In cultured cardiac fibroblasts, TGF\u2010\u03b2 increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. Further, overexpression of Prrx2 or Wnt5a mirrored the effects of TGF\u2010\u03b2 on cell differentiations of cardiac fibroblasts. Gene silence of Wnt5a also ablated cell differentiations induced by Prrx2 overexpression in cardiac fibroblasts. Mechanically, Prrx2 was able to bind with Wnt5a gene promoter to up\u2010regulate Wnt5a gene expression. In conclusions, targeting Prrx2\u2010Wnt5a signalling should be considered to improve cardiac remodelling in patients with ischaemic heart diseases.<\/jats:p>","DOI":"10.1111\/jcmm.14914","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T13:54:41Z","timestamp":1577454881000},"page":"2319-2329","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Up\u2010regulation of paired\u2010related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a"],"prefix":"10.1111","volume":"24","author":[{"given":"Wen\u2010Wu","family":"Bai","sequence":"first","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine Qilu 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