{"id":5157,"date":"2025-10-09T09:09:32","date_gmt":"2025-10-09T07:09:32","guid":{"rendered":"https:\/\/cvja.co.za\/journal\/?p=5157"},"modified":"2025-10-09T09:09:32","modified_gmt":"2025-10-09T07:09:32","slug":"cvja-2025-052","status":"publish","type":"post","link":"https:\/\/cvja.co.za\/journal\/cvja-2025-052\/","title":{"rendered":"Kr\u00fcppel-like factor 5 transcription factor is a positive regulator of NRG-1 in human coronary artery smooth muscle cells"},"content":{"rendered":"    <div id=\"article\">                                                                                                                        \r\n        <div id=\"title-container\">                                                                                                    \r\n        <div id=\"authors-title\">                                                                                                            \r\n        <!--Aurthors under Title-->                                                                                                            \r\n            \r\nPeidong Cao, Xiaotong Qin, Wenze Fu, Chun Gui                                                                                             \r\n        <\/div>        \r\n<\/div>                                                                                                                            \r\n            <div id=\"copyright\">\r\n        <strong>Copyright:<\/strong> Clinics Cardive Publishing (Pty) Ltd. publisher\r\n        of Cardiovascular Journal of Africa.<\/div>\r\n    <div style=\"clear: both;\"><\/div>                                                                                                                                \r\n        <div id=\"article-abstract\">                                                                                                            \r\n            <div id=\"abstract-title\">                                                                                                        \r\n                    Abstract                                                                                                                \r\n                <\/div>                                                                                                                        \r\n                                                                                                                                \r\n            <div id=\"abstract-content\">                                                                                                        \r\n            <!--Content of Abstract Article-->                                                                                                \r\n            <!--<strong>\"Abstract titles\":<\/strong>-->                                                                                        \r\n            <!--<br\/> at the end of each section!!-->                                                                                        \r\n                                                                                                                                            \r\n        <strong>Background:<\/strong>                                                                                                    \r\n                                                                                                                                                    \r\nStructural remodelling of the heart and blood vessels is an important basis for the development of cardiovascular disease. Kr\u00fcppel-like factor 5 (KLF5), an important regulator of cardiovascular remodelling, promotes vascular smooth muscle cell (VSMC) proliferation and inflammatory responses. Neuregulin 1 (NRGI) is a positive regulator of angiogenesis, and its receptors are human epidermal growth factor receptors ErbB2, ErbB3, and ErbB4, which constitute the NRG1\/ErbB signalling system. However, the relationship between the mechanism by which KLF5 promotes smooth muscle cell proliferation and the role of NRGI has not been elucidated                                                                                                \r\n                <br \/>                                                                                                                            \r\n                                                                                                                                                \r\n        <strong>Materials and methods:<\/strong>                                                                                                    \r\n                                                                                                                                                    \r\nHuman coronary artery smooth muscle cells (HCASMCs) were cultured, and DNA fragments specifically enriched for binding to KLF5 proteins in HCASMCs. These were sequenced and analysed by chromatin immunoprecipitation sequencing (ChIP-seq), and downstream proteins NRG1 that could be regulated by KLF5 were identified. Dual luciferase assay was performed to verify whether KLF5 regulated the expression of NRGI, and HCASMC was transfected using KLF5 lentivirus, which was further verified by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. To examine the function of the KLF5\/NRG1\/ErbB pathway in VSMC proliferation, we performed VSMC proliferation assays utilising ErbB2\/3\/4 receptor blockers                                                                                                   \r\n                <br \/>        \r\n                \r\n                <strong>Results:<\/strong>                                                                                                    \r\nNRG is a direct transcriptional target gene of KLF5. KLF5 was able to promote the mRNA and protein expression of NRG1 in HCASMC, blocking ErbB2\/3\/4 receptors, and the role of KLF5 in promoting smooth muscle cell proliferation was attenuated.\r\n                <br \/>\r\n                                                                                                                                                                                                                                                                        \r\n                                                                                                                                                \r\n        <strong>Conclusion:<\/strong>                                                                                                    \r\n                                                                                                                                                    \r\nKLF5 may be one of the mechanisms by which VSMC proliferation may be promoted by upregulating the NRG1\/ErbB pathway.                                                                                                 \r\n                <br \/>        \r\n\r\n                                                                                                                                                \r\n            <\/div>                                                                                                                            \r\n        <\/div>                                                                                                                                    \r\n                                                                                                                                        \r\n                                                                                                                                                \r\n        <div id=\"keywords\">                                                                                                                    \r\n                                                                                                                                            \r\n            <strong>Keywords:<\/strong>                                                                                                        \r\n                                                                                                                                            \r\n            <strong>Kr\u00fcppel-like factor 5, neuregulin 1, ErbB, human coronary artery smooth muscle cell<\/strong>                                                                                                                                                                                                                    \r\n                                                                                                                                                \r\n        <\/div>                                                                                                                                    \r\n                                                                                                                                                \r\n    <div id=\"publish-info\">                                                                                                                    \r\n                                                                                                                                \r\n    <strong>Submitted:<\/strong> May 8, 2024; <!--Month day, year; -->    \r\n    <strong>Accepted:<\/strong> April 23, 2025; <!--Month day, year; -->                                                                            \r\n    <strong>Published:<\/strong> September 26, 2025<!--Month day, year; -->                                                                                                                            <br \/>                                                            \r\n        <em>Cardiovasc J Afr 2025; <b>36<\/b>: 396-402<!--pg no. till pg no. \"eg. 4-7\"--><\/em>\r\n        <br \/><strong>Volume 36, Issue 3<\/strong> <br \/>                                                                            \r\n        <\/div>                                                                                                                            \r\n                                                                                                                                        \r\n    <div id=\"DOI\">                                                                                                                    \r\n            DOI Citation Reference: dx.doi.org\/10.5830\/CVJA-2025-052<!--DOI number-->                                                                \r\n        <\/div>                                                                                                                            \r\n                \r\n                <div id=\"author-affiliation\">                                                                                                \r\n                                                                                                                                        \r\n                <strong>Taicang Branch of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Taicang Loujiang New City Hospital)\r\n<\/strong>    <br \/>                                                                            \r\nPeidong Cao\r\n<br \/><br \/>\r\n\r\n                <strong>Qingdao West Coast New Area District Hospital\r\n<\/strong>    <br \/>                                                                            \r\nXiaotong Qin<br \/>\r\nWenze Fu\r\n<br \/><br \/>\r\n\r\n                <strong>Guangxi Medical University, The First Affiliated Hospital of Guangxi Medical University\r\n\r\n<\/strong>    <br \/>                                                                            \r\nChun Gui\r\n\r\n<br \/><br \/>\r\n                                                                                                                                                                                                                                        \r\n\r\n                [soshsc hide=\"logged\"]\r\n                <strong>You need to be <a style=\"color: #c80c44;\" href=\"https:\/\/cvja.co.za\/journal\/member-login\/\" target=\"_blank\" rel=\"noopener\">logged in to view and download<\/a> the full text PDF version. <a style=\"color: #c80c44;\" href=\"https:\/\/cvja.co.za\/journal\/register\/\" target=\"_blank\" rel=\"noopener\">Register for a free account?<\/a><\/strong> <br \/><br \/>[\/soshsc]\r\n                \r\n                \r\n                \r\n                <\/div>\r\n    \r\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Structural remodelling of the heart and blood vessels is an important basis for the development of cardiovascular disease. Kr\u00fcppel-like factor 5 (KLF5), an important regulator of cardiovascular remodelling, promotes vascular smooth muscle cell (VSMC) proliferation and inflammatory responses. Neuregulin 1 (NRGI) is a positive regulator of angiogenesis, and its receptors are human epidermal growth factor receptors ErbB2, ErbB3, and ErbB4, which constitute the NRG1\/ErbB signalling system. However, the relationship between the mechanism by which KLF5 promotes smooth muscle cell proliferation and the role of NRGI has not been elucidated<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[44,107],"tags":[],"class_list":["post-5157","post","type-post","status-publish","format-standard","hentry","category-cardiovascular-topics","category-volume-36-issue-3"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.0 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Kr\u00fcppel-like factor 5 transcription factor is a positive regulator of NRG-1 in human coronary artery smooth muscle cells - Cardiovascular Journal of Africa<\/title>\n<meta name=\"description\" content=\"Structural remodelling of the heart and blood vessels is an important basis for the development of cardiovascular disease. Kr\u00fcppel-like factor 5 (KLF5), an important regulator of cardiovascular remodelling, promotes vascular smooth muscle cell (VSMC) proliferation and inflammatory responses. Neuregulin 1 (NRGI) is a positive regulator of angiogenesis, and its receptors are human epidermal growth factor receptors ErbB2, ErbB3, and ErbB4, which constitute the NRG1\/ErbB signalling system. However, the relationship between the mechanism by which KLF5 promotes smooth muscle cell proliferation and the role of NRGI has not been elucidated\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/cvja.co.za\/journal\/cvja-2025-052\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Kr\u00fcppel-like factor 5 transcription factor is a positive regulator of NRG-1 in human coronary artery smooth muscle cells - Cardiovascular Journal of Africa\" \/>\n<meta property=\"og:description\" content=\"Structural remodelling of the heart and blood vessels is an important basis for the development of cardiovascular disease. Kr\u00fcppel-like factor 5 (KLF5), an important regulator of cardiovascular remodelling, promotes vascular smooth muscle cell (VSMC) proliferation and inflammatory responses. Neuregulin 1 (NRGI) is a positive regulator of angiogenesis, and its receptors are human epidermal growth factor receptors ErbB2, ErbB3, and ErbB4, which constitute the NRG1\/ErbB signalling system. However, the relationship between the mechanism by which KLF5 promotes smooth muscle cell proliferation and the role of NRGI has not been elucidated\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cvja.co.za\/journal\/cvja-2025-052\/\" \/>\n<meta property=\"og:site_name\" content=\"Cardiovascular Journal of Africa\" \/>\n<meta property=\"article:published_time\" content=\"2025-10-09T07:09:32+00:00\" \/>\n<meta name=\"author\" content=\"Jaco Moolman\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Jaco Moolman\" \/>\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\":\"WebPage\",\"@id\":\"https:\/\/cvja.co.za\/journal\/cvja-2025-052\/\",\"url\":\"https:\/\/cvja.co.za\/journal\/cvja-2025-052\/\",\"name\":\"Kr\u00fcppel-like factor 5 transcription factor is a positive regulator of NRG-1 in human coronary artery smooth muscle cells - Cardiovascular Journal of Africa\",\"isPartOf\":{\"@id\":\"https:\/\/cvja.co.za\/journal\/#website\"},\"datePublished\":\"2025-10-09T07:09:32+00:00\",\"author\":{\"@id\":\"https:\/\/cvja.co.za\/journal\/#\/schema\/person\/6bf8a30a039e93fd8112db707affb920\"},\"description\":\"Structural remodelling of the heart and blood vessels is an important basis for the development of cardiovascular disease. Kr\u00fcppel-like factor 5 (KLF5), an important regulator of cardiovascular remodelling, promotes vascular smooth muscle cell (VSMC) proliferation and inflammatory responses. Neuregulin 1 (NRGI) is a positive regulator of angiogenesis, and its receptors are human epidermal growth factor receptors ErbB2, ErbB3, and ErbB4, which constitute the NRG1\/ErbB signalling system. 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Kr\u00fcppel-like factor 5 (KLF5), an important regulator of cardiovascular remodelling, promotes vascular smooth muscle cell (VSMC) proliferation and inflammatory responses. Neuregulin 1 (NRGI) is a positive regulator of angiogenesis, and its receptors are human epidermal growth factor receptors ErbB2, ErbB3, and ErbB4, which constitute the NRG1\/ErbB signalling system. 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