{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T07:34:12Z","timestamp":1770017652248,"version":"3.49.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The CEMIP (cell migration\u2013inducing protein) exhibits extremely high expression levels in smooth muscle tissues. However, whether CEMIP modulates the contractile phenotype of vascular smooth muscle cells and confers blood pressure remains elusive.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              To explore the role of CEMIP in SMCs, we generated a mouse model with SMC-specific CEMIP deficiency (SMC-\n              <jats:italic toggle=\"yes\">Cemip<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">KO<\/jats:italic>\n              <\/jats:sup>\n              ). By combining coimmunoprecipitation assay and molecular docking prediction, we identified MLC20 (myosin light chain 20) and its phosphatase, PP1c (protein phosphatase 1c) as binding proteins for CEMIP. To elucidate the mechanism by which CEMIP interacts with MLC20 and PP1c, bioluminescence resonance energy transfer assay and motif mutation were utilized to unravel the intricate network.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              CEMIP is abundantly expressed in smooth muscle tissues including the mesenteric artery, aorta, and intestine. In a serum-starved contractile phenotype, SMCs responded to serum stimulation by gradually decreasing CEMIP expression, as they shifted to a secretory phenotype. The mice lacking CEMIP in SMCs showed significantly reduced contractility and blood pressure compared with their counterparts of age-matched wild-type littermates (\n              <jats:italic toggle=\"yes\">Cemip<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">flox\/flox<\/jats:italic>\n              <\/jats:sup>\n              ). Mechanistically, we demonstrated that CEMIP directly interacted with MLC20 to maintain its phosphorylation. In addition, CEMIP sequestered MLC20 from its phosphatase, PP1c, without affecting the kinase MLCK (myosin light chain kinase). Moreover, CEMIP contains 3 critical RVxF (consensus sequence RxxQV\/I\/LK\/RxY\/W) motifs that are responsible for binding to PP1c. Mutations in these motifs restored the interaction between PP1c and MLC20.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>CEMIP functions as a gatekeeper for maintaining the contractile phenotype of SMCs via the PP1c-MLC20 cascade. CEMIP is indispensable for maintaining blood pressure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.125.326233","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:00:13Z","timestamp":1751346013000},"page":"519-532","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["CEMIP Maintains Vascular Contractility by Controlling PP1c-MLC20 Cascade in SMCs"],"prefix":"10.1161","volume":"137","author":[{"given":"Ze","family":"Yuan","sequence":"first","affiliation":[{"name":"The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics (Z.Y., J.H., D.A., Y.Z., B.L.), Tianjin Medical University, China."},{"name":"NHC Key Laboratory of Hormones and Development (Z.Y., J.H., D.A., Y.Z., B.L.), Tianjin Medical University, China."},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) and Department of Physiology and Pathophysiology (Z.Y., J.H., D.A., Y.Z., B.L.), Tianjin Medical University, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Panzhihua Central Hospital, Sichuan, China (Q.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology (X.B., K.Z.), Tianjin Medical University, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2800-0531","authenticated-orcid":true,"given":"Kai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology (X.B., K.Z.), Tianjin Medical University, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7349-8135","authenticated-orcid":true,"given":"Jinlong","family":"He","sequence":"additional","affiliation":[{"name":"The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics (Z.Y., J.H., D.A., Y.Z., B.L.), Tianjin Medical University, China."},{"name":"NHC Key Laboratory of Hormones and Development (Z.Y., J.H., D.A., Y.Z., B.L.), Tianjin Medical University, China."},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) and Department of Physiology and Pathophysiology (Z.Y., J.H., D.A., Y.Z., B.L.), Tianjin Medical University, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5992-9904","authenticated-orcid":true,"given":"Ding","family":"Ai","sequence":"additional","affiliation":[{"name":"The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics (Z.Y., J.H., D.A., Y.Z., B.L.), Tianjin Medical University, China."},{"name":"NHC Key Laboratory of Hormones and Development (Z.Y., J.H., D.A., Y.Z., B.L.), Tianjin Medical University, China."},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) and Department of Physiology and Pathophysiology (Z.Y., J.H., D.A., Y.Z., B.L.), Tianjin Medical University, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-5221","authenticated-orcid":true,"given":"Qinghua","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, China (Q.C.)."},{"name":"School of Sports Medicine, Wuhan Sports University, Hubei Province, China 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