{"id":107373,"date":"2021-07-02T11:12:04","date_gmt":"2021-07-02T15:12:04","guid":{"rendered":"https:\/\/med.virginia.edu\/cell-biology\/?p=107373"},"modified":"2026-05-21T14:22:17","modified_gmt":"2026-05-21T18:22:17","slug":"the-cell-surface-receptors-ror1-2-control-cardiac-myofibroblast-differentiation","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/cell-biology\/2021\/07\/02\/the-cell-surface-receptors-ror1-2-control-cardiac-myofibroblast-differentiation\/","title":{"rendered":"The Cell Surface Receptors Ror1\/2 Control Cardiac Myofibroblast Differentiation"},"content":{"rendered":"<p><strong>UVA Author:<\/strong> Karen Hirschi<br \/>\n<strong>Citation:<\/strong> Chavkin NW, Sano S, Wang Y, et al. The Cell Surface Receptors Ror1\/2 Control Cardiac Myofibroblast Differentiation. J Am Heart Assoc. 2021;10(13):e019904. doi:10.1161\/JAHA.120.019904<\/p>\n<p><strong>DOI:<\/strong><br \/>\n<strong>Pub-Med Number<\/strong>: 34155901<\/p>\n<hr \/>\n<p>Background A hallmark of heart failure is cardiac fibrosis, which results from the injury-induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early proinflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase-like orphan receptor 1 and 2 (Ror1\/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1\/2 in a model of heart failure with emphasis on myofibroblast differentiation. Methods and Results The role of Ror1\/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after transverse aortic constriction surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1\/2 knockout mice displayed a proinflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1\/2 in mice did not result in a detectable baseline phenotype, transverse aortic constriction surgery led to the death of all mice by day 6 that was associated with myocardial hyperinflammation and vascular leakage. Conclusions Together, these results show that Ror1\/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>UVA Author: Karen Hirschi Citation: Chavkin NW, Sano S, Wang Y, et al. The Cell Surface Receptors Ror1\/2 Control Cardiac Myofibroblast Differentiation. J Am Heart Assoc. 2021;10(13):e019904. doi:10.1161\/JAHA.120.019904 DOI: Pub-Med Number: 34155901 Background A hallmark of heart failure is cardiac fibrosis, which results from the injury-induced differentiation response of resident fibroblasts to myofibroblasts that deposit [&hellip;]<\/p>\n","protected":false},"author":1740,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_members_access_role":[],"_members_access_error":"","_links_to":"","_links_to_target":""},"categories":[13],"tags":[21],"class_list":["post-107373","post","type-post","status-publish","format-standard","hentry","category-featured-publications","tag-delete"],"acf":false,"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>The Cell Surface Receptors Ror1\/2 Control Cardiac Myofibroblast Differentiation - Department of Cell Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/med.virginia.edu\/cell-biology\/2021\/07\/02\/the-cell-surface-receptors-ror1-2-control-cardiac-myofibroblast-differentiation\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The Cell Surface Receptors Ror1\/2 Control Cardiac Myofibroblast Differentiation - Department of Cell Biology\" \/>\n<meta property=\"og:description\" content=\"UVA Author: Karen Hirschi Citation: Chavkin NW, Sano S, Wang Y, et al. 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J Am Heart Assoc. 2021;10(13):e019904. doi:10.1161\/JAHA.120.019904 DOI: Pub-Med Number: 34155901 Background A hallmark of heart failure is cardiac fibrosis, which results from the injury-induced differentiation response of resident fibroblasts to myofibroblasts that deposit [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/med.virginia.edu\/cell-biology\/2021\/07\/02\/the-cell-surface-receptors-ror1-2-control-cardiac-myofibroblast-differentiation\/\" \/>\n<meta property=\"og:site_name\" content=\"Department of Cell Biology\" \/>\n<meta property=\"article:published_time\" content=\"2021-07-02T15:12:04+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-05-21T18:22:17+00:00\" \/>\n<meta name=\"author\" content=\"zkr7e@virginia.edu\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"zkr7e@virginia.edu\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2021\\\/07\\\/02\\\/the-cell-surface-receptors-ror1-2-control-cardiac-myofibroblast-differentiation\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2021\\\/07\\\/02\\\/the-cell-surface-receptors-ror1-2-control-cardiac-myofibroblast-differentiation\\\/\"},\"author\":{\"name\":\"zkr7e@virginia.edu\",\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/#\\\/schema\\\/person\\\/b4929a1d4683383a392718e12166cd7f\"},\"headline\":\"The Cell Surface Receptors Ror1\\\/2 Control Cardiac Myofibroblast Differentiation\",\"datePublished\":\"2021-07-02T15:12:04+00:00\",\"dateModified\":\"2026-05-21T18:22:17+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2021\\\/07\\\/02\\\/the-cell-surface-receptors-ror1-2-control-cardiac-myofibroblast-differentiation\\\/\"},\"wordCount\":288,\"keywords\":[\"Delete\"],\"articleSection\":[\"Featured Publications\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2021\\\/07\\\/02\\\/the-cell-surface-receptors-ror1-2-control-cardiac-myofibroblast-differentiation\\\/\",\"url\":\"https:\\\/\\\/med.virginia.edu\\\/cell-biology\\\/2021\\\/07\\\/02\\\/the-cell-surface-receptors-ror1-2-control-cardiac-myofibroblast-differentiation\\\/\",\"name\":\"The Cell Surface Receptors Ror1\\\/2 Control Cardiac Myofibroblast Differentiation - 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