BMP7 Ameliorated Viral Myocardial Fibrosis by Inhibiting Endothelial-to-Mesenchymal Transition

BMP7 Ameliorated Viral Myocardial Fibrosis by Inhibiting Endothelial-to-Mesenchymal Transition | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research BMP7 Ameliorated Viral Myocardial Fibrosis by Inhibiting Endothelial-to-Mesenchymal Transition Yeqing Xie, Jianquan Liao, Yong Yu, Ruizhen Chen, Xiaoqiang Ding This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-132246/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Endothelial-to-mesenchymal transition (Endo-MT) is associated with myocardial fibrosis in dilated cardiomyopathy (DCM). Endothelial-to-mesenchymal transition (Endo-MT) is induced by coxsackievirus B3 (CVB3) in cardiac microvascular endothelial cells (CMVECs). Bone morphogenetic protein 7 (BMP7) significantly inhibits Endo-MT and the progression of cardiac fibrosis. The study was aimed to investigate the effect and the underlying mechanism of BMP7 on Endo-MT in myocardial fibrosis induce by CVB3 infection in vivo. Methods: BALB/c mice were intraperitoneally injected by CVB3 to induce viral myocarditis (VMC). Mice were treated with BMP7 after CVB3 infection. Subsequently, all groups of mice were determined by echocardiography, histopathologic and molecular detection. Results: We found that the ratio of BMP7/TGF-β1 in mRNA levels was decreased obviously at different time points after CVB3 injection. BMP7 facilitated the recovery of cardiac function after CVB3 infection via inhibition of myocardial damage, collagen deposition. Double immunofluorescence staining indicated that Endo-MT was implicated in CVB3-induced myocardial fibrosis, which was attenuated by BMP7. The protein levels of pSmad3 and Smad4 were significantly upregulated in VMC group, as well as Wnt/β-catenin and the transcription factor snail. BMP7 treatment reversed the changes of these protein levels. Moreover, CO-IP demonstrated the crosstalk between β-catenin and Smad3 in VMC mice, which was downregulated by BMP7 treatment. Conclusions: These results indicated that BMP7 obviously ameliorated myocardial fibrosis in CVB3-infected mice via Endo-MT, which was involved in the TGF-β/Smad and Wnt/β-catenin pathway. β-Catenin/Smad3 interaction may be associated with Endo-MT in the development of viral myocardial fibrosis. Translational Medicine Viral myocarditis endothelial-to-mesenchymal transition cardiac fibrosis BMP7 Wnt/β-catenin TGF-β1/Smads Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Full Text Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and accessed as a PDF. Tables Table 1: Mortality and echo results of three groups Control VMC VMC+BMP7 Survival mice/Total mice 10/10 12/20 15/20 Mortality(%) 0 40 25 LVEDd(mm) 3.05±0.23 4.27±0.19 * 3.58±0.21 § LVEDs(mm) 1.16±0.12 2.79±0.15 * 1.78±0.09 § LVEF (%) 94.04±5.12 56.01±2.56 * 84.49±4.79 § FS (%) 67.05±3.45 28.83±1.89 * 52.86±2.97 § * VMC group vs Control group, p <0.05 §VMC+BMP7 group vs VMC group, p <0.05 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-132246","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":6781672,"identity":"f8e36029-1a71-4e03-a693-f851dac6789f","order_by":0,"name":"Yeqing Xie","email":"","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yeqing","middleName":"","lastName":"Xie","suffix":""},{"id":6781673,"identity":"c7c304e2-c14f-411b-a3c0-58b8b98cbb82","order_by":1,"name":"Jianquan Liao","email":"","orcid":"","institution":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032，China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianquan","middleName":"","lastName":"Liao","suffix":""},{"id":6781674,"identity":"4025de58-49a1-4527-a1b1-211ef92968b9","order_by":2,"name":"Yong Yu","email":"","orcid":"","institution":"Key Laboratory of Viral Heart Diseases, Ministry of Public Health，Shanghai Institute of Cardiovascular Diseases，Zhongshan Hospital，Fudan University，Shanghai 200032，China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yong","middleName":"","lastName":"Yu","suffix":""},{"id":6781675,"identity":"c23cf87a-0b65-455b-973b-9f8cf1143cfd","order_by":3,"name":"Ruizhen Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYDACCShpwMDA+CChQkKOjb35ANFamA0+nLEx5uM5lkCMFgaQFjbJmW1pifMkchTw6uCf3XzscWWbhb05e+8BaR62w+ltDDkMDD8qtuG25M6xdMOzbRLMlj3nEox5eA7ntjGcPcDYc+Y2Ti0GEjlmko1tEmwGN3IMknkkgFoY+xKYGdvwacn/BtLCY3D/jcFhHoPD6WzMPAYEtOSwgbRIGNzgMWyckZCWwMZGQIvEjTQzyYZzEgYGZ3KMGT4csDFs42FLOIjPL/wzkp9JNpTV2RscP2P+I/GfhLz8/McHH/yowK0FOzhAovpRMApGwSgYBWgAAMUAUt8UOW9RAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-4449-0449","institution":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032，China","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ruizhen","middleName":"","lastName":"Chen","suffix":""},{"id":6781676,"identity":"4575ef27-6645-4fe5-ba2f-31cd1d834c8c","order_by":4,"name":"Xiaoqiang Ding","email":"","orcid":"","institution":"Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032，China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaoqiang","middleName":"","lastName":"Ding","suffix":""}],"badges":[],"createdAt":"2020-12-19 13:08:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-132246/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-132246/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":4555718,"identity":"3b4f3ac5-066f-4d7d-b063-596a51a6ddaa","added_by":"auto","created_at":"2020-12-28 20:29:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":69066,"visible":true,"origin":"","legend":"BMP7 to TGF-β1 ratio was on decline trend in mRNA levels at different time points after CVB3 injection. ","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1/eb01bb976a3e738bf43ab1f2.png"},{"id":4555816,"identity":"861084fa-33f1-49f0-9c42-964323d925bc","added_by":"auto","created_at":"2020-12-28 20:32:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":474171,"visible":true,"origin":"","legend":" As echo demonstrated, impaired cardiac function with increased parameters of LVEDd and LVEDs and declined LVEF and FS was found in VMC group, which was attenuated by BMP7 administration. * VMC group vs Control group, p\u003c0.05; § VMC+BMP7 group vs VMC group, p\u003c0.05 ","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1/362b7f3238e149568e615da7.png"},{"id":4555719,"identity":"ec844936-e385-4b9f-81e4-c02044a71ec6","added_by":"auto","created_at":"2020-12-28 20:29:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":509860,"visible":true,"origin":"","legend":"A. HE and Sirus Red staining of heart tissue of three groups; B. Murine heart weight to body weight ratio; C. Virus replication in cardiac samples after CVB3 injection. * VMC group vs Control group, p\u003c0.05; § VMC+BMP7 group vs VMC group, p\u003c0.05 ","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1/9101d19ced76f92392f47ec8.png"},{"id":4555662,"identity":"9c3250f7-92e4-4aed-8338-d94282da5799","added_by":"auto","created_at":"2020-12-28 20:26:43","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":4519502,"visible":true,"origin":"","legend":" Immunohistochemistry staining of CD31 and FSP-1 in each group. # VMC group vs Control group, p\u003c0.05; § VMC+BMP7 group vs VMC group, p\u003c0.05 ","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1/04ff759002a15c948e04a194.png"},{"id":4555720,"identity":"e7067c8a-6418-4892-b981-96011fb10259","added_by":"auto","created_at":"2020-12-28 20:29:43","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2269508,"visible":true,"origin":"","legend":"Co-localization of endothelial markers and mesenchymal markers. Double immunofluorescence staining of CD31 and αSMA, and VE-cadherin and FSP1 was performed. The expression of CD31 and VE-cadherin were colored with green, and the expression of αSMA and FSP1 were colored with red. Co-labelled of CD31 and αSMA was observed in cardiac endothelial cells of VMC mice, as well as VE-cadherin and FSP1. ","description":"","filename":"figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1/cc1894bd6b56253ee5ab0d7e.png"},{"id":4555722,"identity":"fe10698d-a724-40bf-9633-0fbdd346d61a","added_by":"auto","created_at":"2020-12-28 20:29:43","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":91842,"visible":true,"origin":"","legend":"Western blot demonstrated the upregulated protein levels of pSmad3/Smad3 and Smad4 in VMC group, as well as the elevated protein expression of Wnt, β-catenin and its transcription factor snail. However, those TGF-β1/Smads and Wnt/β-catenin signaling protein have been downregulated after BMP7 intervention. # VMC group vs Control group, p\u003c0.05; § VMC+BMP7 group vs VMC group, p\u003c0.05","description":"","filename":"figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1/cdf3c9d37731aac196ae33fb.png"},{"id":4555667,"identity":"8727f6a6-7f67-4b54-9f8f-5d0dad31ad70","added_by":"auto","created_at":"2020-12-28 20:26:43","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":507754,"visible":true,"origin":"","legend":"Co-IP assay revealed the increased interaction of endogenous β-catenin and smad3 in CVB3-infected mice, which was disrupted by BMP7. ","description":"","filename":"figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1/be4e2192a4c911bee2c96002.png"},{"id":4555665,"identity":"5a413297-8367-45e9-bfb0-09d8939b97ab","added_by":"auto","created_at":"2020-12-28 20:26:43","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":949458,"visible":true,"origin":"","legend":"Schematic diagram of the protective effect of BMP7 against Endo-MT and cardiac fibrosis. ","description":"","filename":"figure8.png","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1/db5951b25d9335a5ab1df8fe.png"},{"id":13568925,"identity":"d8766338-906c-4c44-a9bd-992ef4510078","added_by":"auto","created_at":"2021-09-17 03:38:08","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":905337,"visible":true,"origin":"","legend":"","description":"","filename":"MSJTM.pdf","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1_covered.pdf"},{"id":4555864,"identity":"81fbdf8f-4d80-470b-aa18-dde2949850fb","added_by":"auto","created_at":"2020-12-28 20:35:47","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1168818,"visible":true,"origin":"","legend":"","description":"","filename":"MSJTM.pdf","url":"https://assets-eu.researchsquare.com/files/rs-132246/v1_stamped.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eBMP7 Ameliorated Viral Myocardial Fibrosis by Inhibiting Endothelial-to-Mesenchymal Transition\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and \u003ca href='/article/rs-132246/latest.pdf' target='_blank'\u003e accessed as a PDF.\u003c/a\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1: Mortality and echo results of three groups\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003e \u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eControl\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003eVMC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003eVMC+BMP7\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003eSurvival mice/Total mice\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e10/10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003e12/20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e15/20\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003eMortality(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003e40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003eLVEDd(mm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e3.05\u0026plusmn;0.23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003e4.27\u0026plusmn;0.19\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e3.58\u0026plusmn;0.21\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003eLVEDs(mm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e1.16\u0026plusmn;0.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003e2.79\u0026plusmn;0.15\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e1.78\u0026plusmn;0.09\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003eLVEF (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e94.04\u0026plusmn;5.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003e56.01\u0026plusmn;2.56\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e84.49\u0026plusmn;4.79\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"194\"\u003e\n\u003cp\u003eFS (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e67.05\u0026plusmn;3.45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"123\"\u003e\n\u003cp\u003e28.83\u0026plusmn;1.89\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e52.86\u0026plusmn;2.97\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e*\u003c/sup\u003e VMC group \u003cem\u003evs \u003c/em\u003eControl group, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05\u003c/p\u003e\n\u003cp\u003e§VMC+BMP7 group \u003cem\u003evs \u003c/em\u003eVMC group, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Viral myocarditis, endothelial-to-mesenchymal transition, cardiac fibrosis, BMP7, Wnt/β-catenin, TGF-β1/Smads ","lastPublishedDoi":"10.21203/rs.3.rs-132246/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-132246/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Endothelial-to-mesenchymal transition (Endo-MT) is associated with myocardial fibrosis in dilated cardiomyopathy (DCM). Endothelial-to-mesenchymal transition (Endo-MT) is induced by coxsackievirus B3 (CVB3) in cardiac microvascular endothelial cells (CMVECs). Bone morphogenetic protein 7 (BMP7) significantly inhibits Endo-MT and the progression of cardiac fibrosis. The study was aimed to investigate the effect and the underlying mechanism of BMP7 on Endo-MT in myocardial fibrosis induce by CVB3 infection in vivo. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e BALB/c mice were intraperitoneally injected by CVB3 to induce viral myocarditis (VMC). Mice were treated with BMP7 after CVB3 infection. Subsequently, all groups of mice were determined by echocardiography, histopathologic and molecular detection. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e We found that the ratio of BMP7/TGF-β1 in mRNA levels was decreased obviously at different time points after CVB3 injection. BMP7 facilitated the recovery of cardiac function after CVB3 infection via inhibition of myocardial damage, collagen deposition. Double immunofluorescence staining indicated that Endo-MT was implicated in CVB3-induced myocardial fibrosis, which was attenuated by BMP7. The protein levels of pSmad3 and Smad4 were significantly upregulated in VMC group, as well as Wnt/β-catenin and the transcription factor snail. BMP7 treatment reversed the changes of these protein levels. Moreover, CO-IP demonstrated the crosstalk between β-catenin and Smad3 in VMC mice, which was downregulated by BMP7 treatment. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e These results indicated that BMP7 obviously ameliorated myocardial fibrosis in CVB3-infected mice via Endo-MT, which was involved in the TGF-β/Smad and Wnt/β-catenin pathway. β-Catenin/Smad3 interaction may be associated with Endo-MT in the development of viral myocardial fibrosis.\u003c/p\u003e","manuscriptTitle":"BMP7 Ameliorated Viral Myocardial Fibrosis by Inhibiting Endothelial-to-Mesenchymal Transition","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-12-28 20:26:41","doi":"10.21203/rs.3.rs-132246/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fd889f3d-1be3-4d72-83d7-c028f760d3ab","owner":[],"postedDate":"December 28th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":1581108,"name":"Translational Medicine"}],"tags":[],"updatedAt":"2020-12-28T20:26:43+00:00","versionOfRecord":[],"versionCreatedAt":"2020-12-28 20:26:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-132246","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-132246","identity":"rs-132246","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}