{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:17:19Z","timestamp":1792793839004,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000332"],"award-info":[{"award-number":["82000332"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medicine and Engineering Cross"},{"name":"Shanghai Jiaotong University","award":["YG2019QNA56"],"award-info":[{"award-number":["YG2019QNA56"]}],"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Crosstalk between fibroblasts and cardiomyocytes (CMs) plays a critical role in cardiac remodelling during heart failure (HF); however, the underlying molecular mechanisms remain obscure. Recently, a secretory protein, Integrin beta-like 1 (ITGBL1) was revealed to have detrimental effects on several diseases, such as tumours, pulmonary fibrosis, and hepatic fibrosis; whereas the effect of ITGBL1 on HF is unclear. The purpose of this study was to evaluate its contribution to volume overload-induced remodelling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this study, we identified ITGBL1 was highly expressed in varied heart diseases and validated in our TAC mice model, especially in fibroblasts. To investigate the role of ITGBL1 in in vitro cell experiments, neonatal rat fibroblasts (NRCFs) and cardiomyocytes (NRCMs) were performed for further study. We found that in comparison to NRCMs, NRCFs expressed high levels of ITGBL1. Meanwhile, ITGBL1 was upregulated in NRCFs, but not in NRCMs following angiotensin-II (AngII) or phenylephrine stimulation. Furthermore, ITGBL1 overexpression promoted NRCFs activation, whereas knockdown of ITGBL1 alleviated NRCFs activation under AngII treatment. Moreover, NRCFs-secreted ITGBL1 could induce NRCMs hypertrophy. Mechanically, ITGBL1-NME\/NM23 nucleoside diphosphate kinase 1 (NME1)-TGF-\u03b2-Smad2\/3 and Wnt signalling pathways were identified to mediate NRCFs activation and NRCMs hypertrophy, respectively. Finally, the knockdown of ITGBL1 in mice subjected to transverse aortic constriction (TAC) surgery recapitulated the in vitro findings, demonstrating blunted cardiac fibrosis, hypertrophy, and improved cardiac function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ITGBL1 is an important functional mediator between fibroblast\u2013cardiomyocyte crosstalk and could be an effective target for cardiac remodelling in HF patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvad104","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T10:02:32Z","timestamp":1688119352000},"page":"1928-1941","source":"Crossref","is-referenced-by-count":39,"title":["Integrin beta-like 1 mediates fibroblast\u2013cardiomyocyte crosstalk to promote cardiac fibrosis and hypertrophy"],"prefix":"10.1093","volume":"119","author":[{"given":"XiaoQiang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XinTao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoYu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GenQing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6492-5702","authenticated-orcid":false,"given":"SongWen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoFeng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0351-6868","authenticated-orcid":false,"given":"ShaoWen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0796-6048","authenticated-orcid":false,"given":"LiDong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"2023081913255065800_cvad104-B1","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1161\/CIRCULATIONAHA.112.000855","article-title":"H(2)S protects against pressure overload-induced heart failure via upregulation of endothelial nitric oxide synthase","volume":"127","author":"Kondo","year":"2013","journal-title":"Circulation"},{"key":"2023081913255065800_cvad104-B2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41569-018-0007-y","article-title":"Mechanisms of physiological and pathological cardiac hypertrophy","volume":"15","author":"Nakamura","year":"2018","journal-title":"Nat Rev Cardiol"},{"key":"2023081913255065800_cvad104-B3","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41586-020-2586-0","article-title":"Position-specific oxidation of miR-1 encodes cardiac hypertrophy","volume":"584","author":"Seok","year":"2020","journal-title":"Nature"},{"key":"2023081913255065800_cvad104-B4","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/s41467-017-00840-w","article-title":"Loss of beta-catenin in resident cardiac fibroblasts attenuates fibrosis induced by pressure overload in mice","volume":"8","author":"Xiang","year":"2017","journal-title":"Nat Commun"},{"key":"2023081913255065800_cvad104-B5","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1093\/cvr\/cvz234","article-title":"CGRP Derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis","volume":"116","author":"Li","year":"2020","journal-title":"Cardiovasc Res"},{"key":"2023081913255065800_cvad104-B6","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.3390\/cells10071716","article-title":"Cardiac fibrosis and fibroblasts","volume":"10","author":"Kurose","year":"2021","journal-title":"Cells"},{"key":"2023081913255065800_cvad104-B7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00395-016-0598-6","article-title":"Role of integrins in mediating cardiac fibroblast-cardiomyocyte cross talk: a dynamic relationship in cardiac biology and pathophysiology","volume":"112","author":"Civitarese","year":"2017","journal-title":"Basic Res Cardiol"},{"key":"2023081913255065800_cvad104-B8","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1161\/01.RES.81.5.679","article-title":"Trophic effect of human pericardial fluid on adult cardiac myocytes. Differential role of fibroblast growth factor-2 and factors related to ventricular hypertrophy","volume":"81","author":"Corda","year":"1997","journal-title":"Circ Res"},{"key":"2023081913255065800_cvad104-B9","first-page":"143","article-title":"Fibroblast growth factor 2 mediates isoproterenol-induced cardiac hypertrophy through activation of the extracellular regulated kinase","volume":"2","author":"House","year":"2010","journal-title":"Mol Cell Pharmacol"},{"key":"2023081913255065800_cvad104-B10","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.3390\/cancers12092676","article-title":"Evaluation of the role of ITGBL1 in ovarian cancer","volume":"12","author":"Cortez","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2023081913255065800_cvad104-B11","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1006\/geno.1998.5707","article-title":"Cloning and characterization of a novel beta integrin-related cDNA coding for the protein TIED (\u201cten beta integrin EGF-like repeat domains\u201d) that maps to chromosome band 13q33: A divergent stand-alone integrin stalk structure","volume":"56","author":"Berg","year":"1999","journal-title":"Genomics"},{"key":"2023081913255065800_cvad104-B12","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.biopha.2018.05.033","article-title":"ITGBL1 Promotes migration, invasion and predicts a poor prognosis in colorectal cancer","volume":"104","author":"Qiu","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"2023081913255065800_cvad104-B13","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/s41467-020-14869-x","article-title":"Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation","volume":"11","author":"Ji","year":"2020","journal-title":"Nat Commun"},{"key":"2023081913255065800_cvad104-B14","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3233\/CBM-190460","article-title":"Upregulation of ITGBL1 predicts poor prognosis and promotes chemoresistance in ovarian cancer","volume":"27","author":"Song","year":"2020","journal-title":"Cancer Biomark"},{"key":"2023081913255065800_cvad104-B15","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/nature07511","article-title":"MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts","volume":"456","author":"Thum","year":"2008","journal-title":"Nature"},{"key":"2023081913255065800_cvad104-B16","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1172\/JCI30634","article-title":"IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system","volume":"117","author":"Sanada","year":"2007","journal-title":"J Clin Invest"},{"key":"2023081913255065800_cvad104-B17","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/s41419-018-0598-6","article-title":"Nogo-C regulates post myocardial infarction fibrosis through the interaction with ER Ca(2+) leakage channel Sec61alpha in mouse hearts","volume":"9","author":"Weng","year":"2018","journal-title":"Cell Death Dis"},{"key":"2023081913255065800_cvad104-B18","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1161\/CIRCULATIONAHA.121.055727","article-title":"DYRK1B-STAT3 Drives cardiac hypertrophy and heart failure by impairing mitochondrial bioenergetics","volume":"145","author":"Zhuang","year":"2022","journal-title":"Circulation"},{"key":"2023081913255065800_cvad104-B19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s00395-021-00871-x","article-title":"Macrophage depletion in stellate ganglia alleviates cardiac sympathetic overactivation and ventricular arrhythmogenesis by attenuating neuroinflammation in heart failure","volume":"116","author":"Zhang","year":"2021","journal-title":"Basic Res Cardiol"},{"key":"2023081913255065800_cvad104-B20","doi-asserted-by":"crossref","first-page":"12075","DOI":"10.1074\/jbc.M609832200","article-title":"NM23-H1 tumor suppressor physically interacts with serine-threonine kinase receptor-associated protein, a transforming growth factor-beta (TGF-beta) receptor-interacting protein, and negatively regulates TGF-beta signaling","volume":"282","author":"Seong","year":"2007","journal-title":"J Biol Chem"},{"key":"2023081913255065800_cvad104-B21","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1002\/cphy.c140060","article-title":"Wnt signaling in cardiac disease","volume":"5","author":"Hermans","year":"2015","journal-title":"Compr Physiol"},{"key":"2023081913255065800_cvad104-B22","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1161\/CIRCRESAHA.115.306565","article-title":"Cardiac fibrosis: the fibroblast awakens","volume":"118","author":"Travers","year":"2016","journal-title":"Circ Res"},{"key":"2023081913255065800_cvad104-B23","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1172\/JCI40295","article-title":"Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload","volume":"120","author":"Takeda","year":"2010","journal-title":"J Clin Invest"},{"key":"2023081913255065800_cvad104-B24","doi-asserted-by":"crossref","first-page":"43446","DOI":"10.1038\/srep43446","article-title":"Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis","volume":"7","author":"Wang","year":"2017","journal-title":"Sci Rep"},{"key":"2023081913255065800_cvad104-B25","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.ymthe.2018.08.026","article-title":"lncITPF promotes pulmonary fibrosis by targeting hnRNP-L depending on its host gene ITGBL1","volume":"27","author":"Song","year":"2019","journal-title":"Mol Ther"},{"key":"2023081913255065800_cvad104-B26","first-page":"1447","article-title":"Identification of differentially expressed genes and preliminary validations in cardiac pathological remodeling induced by transverse aortic constriction","volume":"44","author":"Wang","year":"2019","journal-title":"Int J Mol Med"},{"key":"2023081913255065800_cvad104-B27","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s00395-021-00862-y","article-title":"Fibroblast GATA-4 and GATA-6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis","volume":"116","author":"Dittrich","year":"2021","journal-title":"Basic Res Cardiol"},{"key":"2023081913255065800_cvad104-B28","doi-asserted-by":"crossref","first-page":"11074","DOI":"10.1038\/ncomms11074","article-title":"The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy","volume":"7","author":"Mohamed","year":"2016","journal-title":"Nat Commun"},{"key":"2023081913255065800_cvad104-B29","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1161\/CIRCRESAHA.108.180976","article-title":"Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy","volume":"104","author":"Jaffre","year":"2009","journal-title":"Circ Res"},{"key":"2023081913255065800_cvad104-B30","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1124\/pr.117.013896","article-title":"WNT signaling in cardiac and vascular disease","volume":"70","author":"Foulquier","year":"2018","journal-title":"Pharmacol Rev"},{"key":"2023081913255065800_cvad104-B31","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1161\/CIRCRESAHA.110.223768","article-title":"WNT signaling in adult cardiac hypertrophy and remodeling: lessons learned from cardiac development","volume":"107","author":"Bergmann","year":"2010","journal-title":"Circ Res"},{"key":"2023081913255065800_cvad104-B32","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.7150\/jca.20900","article-title":"ITGBL1 predicts a poor prognosis and correlates EMT phenotype in gastric cancer","volume":"8","author":"Li","year":"2017","journal-title":"J Cancer"},{"key":"2023081913255065800_cvad104-B33","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3389\/fonc.2020.00259","article-title":"Regulatory mechanism of ITGBL1 in the metastasis of colorectal cancer","volume":"10","author":"Qi","year":"2020","journal-title":"Front Oncol"},{"key":"2023081913255065800_cvad104-B34","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/S0140-6736(19)31674-5","article-title":"Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases","volume":"394","author":"Strongman","year":"2019","journal-title":"Lancet"},{"key":"2023081913255065800_cvad104-B35","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41569-019-0286-y","article-title":"Heart failure as interstitial cancer: emergence of a malignant fibroblast phenotype","volume":"17","author":"Oatmen","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"2023081913255065800_cvad104-B36","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1002\/ejhf.2207","article-title":"The association between heart failure and incident cancer in women: an analysis of the Women\u2019s Health Initiative","volume":"23","author":"Leedy","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"2023081913255065800_cvad104-B37","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.jacc.2013.04.088","article-title":"Patients with heart failure have an increased risk of incident cancer","volume":"62","author":"Hasin","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"2023081913255065800_cvad104-B38","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1161\/CIRCRESAHA.121.319314","article-title":"The cancer therapy-related clonal hematopoiesis driver gene Ppm1d promotes inflammation and non-ischemic heart failure in mice","volume":"129","author":"Yura","year":"2021","journal-title":"Circ Res"},{"key":"2023081913255065800_cvad104-B39","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1161\/CIRCULATIONAHA.118.033603","article-title":"Linking heart failure to cancer: background evidence and research perspectives","volume":"138","author":"Bertero","year":"2018","journal-title":"Circulation"}],"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvad104\/50857219\/cvad104.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/119\/10\/1928\/51174576\/cvad104.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/119\/10\/1928\/51174576\/cvad104.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T09:26:19Z","timestamp":1692437179000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/119\/10\/1928\/7216985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,3]]},"references-count":39,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,7,3]]},"published-print":{"date-parts":[[2023,8,19]]}},"URL":"https:\/\/doi.org\/10.1093\/cvr\/cvad104","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,8]]},"published":{"date-parts":[[2023,7,3]]}}}