{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:51:17Z","timestamp":1789843877587,"version":"4.0.1"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eBioMedicine"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1016\/j.ebiom.2022.104274","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T05:20:50Z","timestamp":1664342450000},"page":"104274","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":43,"special_numbering":"C","title":["Inhibition of HIPK2 protects stress-induced pathological cardiac remodeling"],"prefix":"10.1016","volume":"85","author":[{"given":"Qiulian","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost P.G.","family":"Sluijter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9386","key":"10.1016\/j.ebiom.2022.104274_bib0001","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/S0140-6736(03)14284-5","article-title":"Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial","volume":"362","author":"Granger","year":"2003","journal-title":"Lancet"},{"issue":"6","key":"10.1016\/j.ebiom.2022.104274_bib0002","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.jshs.2021.08.002","article-title":"Animal exercise studies in cardiovascular research: Current knowledge and optimal design-A position paper of the committee on cardiac rehabilitation, Chinese medical doctors' association","volume":"10","author":"Bei","year":"2021","journal-title":"J Sport Health Sci"},{"issue":"3","key":"10.1016\/j.ebiom.2022.104274_bib0003","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1161\/CIRCULATIONAHA.119.042178","article-title":"A novel role of cyclic nucleotide phosphodiesterase 10A in pathological cardiac remodeling and dysfunction","volume":"141","author":"Chen","year":"2020","journal-title":"Circulation"},{"issue":"1","key":"10.1016\/j.ebiom.2022.104274_bib0004","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.1038\/s41467-019-12748-8","article-title":"Injectable human recombinant collagen matrices limit adverse remodeling and improve cardiac function after myocardial infarction","volume":"10","author":"McLaughlin","year":"2019","journal-title":"Nat Commun"},{"issue":"6","key":"10.1016\/j.ebiom.2022.104274_bib0005","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jshs.2021.11.001","article-title":"Exercise and cardiovascular protection: update and future","volume":"10","author":"Xiao","year":"2021","journal-title":"J Sport Health Sci"},{"issue":"3","key":"10.1016\/j.ebiom.2022.104274_bib0006","doi-asserted-by":"crossref","first-page":"178","DOI":"10.2174\/2211536607666180525102330","article-title":"Update on the regulation of HIPK1, HIPK2 and HIPK3 protein kinases by microRNAs","volume":"7","author":"Conte","year":"2018","journal-title":"Microrna"},{"issue":"40","key":"10.1016\/j.ebiom.2022.104274_bib0007","doi-asserted-by":"crossref","first-page":"25875","DOI":"10.1074\/jbc.273.40.25875","article-title":"Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors","volume":"273","author":"Kim","year":"1998","journal-title":"J Biol Chem"},{"issue":"2","key":"10.1016\/j.ebiom.2022.104274_bib0008","article-title":"HIPK2 modification code for cell death and survival","volume":"1","author":"Wook Choi","year":"2014","journal-title":"Mol Cell Oncol"},{"issue":"2","key":"10.1016\/j.ebiom.2022.104274_bib0009","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/cdd.2013.160","article-title":"Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing Groucho\/TLE:Hes1-mediated inhibition of neuronal differentiation","volume":"21","author":"Ciarapica","year":"2014","journal-title":"Cell Death Differ"},{"issue":"11","key":"10.1016\/j.ebiom.2022.104274_bib0010","doi-asserted-by":"crossref","first-page":"5731","DOI":"10.1093\/nar\/gkt262","article-title":"Homeodomain-interacting protein kinase 2-dependent repression of myogenic differentiation is relieved by its caspase-mediated cleavage","volume":"41","author":"de la Vega","year":"2013","journal-title":"Nucleic Acids Res"},{"issue":"20","key":"10.1016\/j.ebiom.2022.104274_bib0011","doi-asserted-by":"crossref","first-page":"7373","DOI":"10.1073\/pnas.1322275111","article-title":"Identification of Hipk2 as an essential regulator of white fat development","volume":"111","author":"Sjolund","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"39","key":"10.1016\/j.ebiom.2022.104274_bib0012","doi-asserted-by":"crossref","first-page":"13746","DOI":"10.1523\/JNEUROSCI.1078-11.2011","article-title":"Homeodomain interacting protein kinase 2 regulates postnatal development of enteric dopaminergic neurons and glia via BMP signaling","volume":"31","author":"Chalazonitis","year":"2011","journal-title":"J Neurosci"},{"issue":"4","key":"10.1016\/j.ebiom.2022.104274_bib0013","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nm.2685","article-title":"A systems approach identifies HIPK2 as a key regulator of kidney fibrosis","volume":"18","author":"Jin","year":"2012","journal-title":"Nat Med"},{"issue":"7","key":"10.1016\/j.ebiom.2022.104274_bib0014","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1681\/ASN.2016080841","article-title":"A novel inhibitor of homeodomain interacting protein kinase 2 mitigates kidney fibrosis through inhibition of the TGF-beta1\/Smad3 pathway","volume":"28","author":"Liu","year":"2017","journal-title":"J Am Soc Nephrol"},{"issue":"32","key":"10.1016\/j.ebiom.2022.104274_bib0015","doi-asserted-by":"crossref","first-page":"13040","DOI":"10.1073\/pnas.0703213104","article-title":"HIPK2 represses beta-catenin-mediated transcription, epidermal stem cell expansion, and skin tumorigenesis","volume":"104","author":"Wei","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"22","key":"10.1016\/j.ebiom.2022.104274_bib0016","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1161\/CIRCULATIONAHA.119.040740","article-title":"Cardiomyocyte homeodomain-interacting protein kinase 2 maintains basal cardiac function via extracellular signal-regulated kinase signaling","volume":"140","author":"Guo","year":"2019","journal-title":"Circulation"},{"issue":"4","key":"10.1016\/j.ebiom.2022.104274_bib0017","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.cmet.2015.02.014","article-title":"miR-222 is necessary for exercise-induced cardiac growth and protects against pathological cardiac remodeling","volume":"21","author":"Liu","year":"2015","journal-title":"Cell Metab"},{"key":"10.1016\/j.ebiom.2022.104274_bib0018","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2021.103713","article-title":"Exercise downregulates HIPK2 and HIPK2 inhibition protects against myocardial infarction","volume":"74","author":"Zhou","year":"2021","journal-title":"EBioMedicine"},{"issue":"2","key":"10.1016\/j.ebiom.2022.104274_bib0019","doi-asserted-by":"crossref","first-page":"e89176","DOI":"10.1371\/journal.pone.0089176","article-title":"Synthesis and properties of a selective inhibitor of homeodomain-interacting protein kinase 2 (HIPK2)","volume":"9","author":"Cozza","year":"2014","journal-title":"PLoS One"},{"issue":"7","key":"10.1016\/j.ebiom.2022.104274_bib0020","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.chembiol.2011.05.010","article-title":"High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors","volume":"18","author":"Miduturu","year":"2011","journal-title":"Chem Biol"},{"issue":"5","key":"10.1016\/j.ebiom.2022.104274_bib0021","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1161\/CIRCRESAHA.117.310624","article-title":"Inhibition of the cardiac fibroblast-enriched lncRNA Meg3 prevents cardiac fibrosis and diastolic dysfunction","volume":"121","author":"Piccoli","year":"2017","journal-title":"Circ Res"},{"issue":"1","key":"10.1016\/j.ebiom.2022.104274_bib0022","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12916-019-1268-y","article-title":"Cathelicidin-related antimicrobial peptide protects against myocardial ischemia\/reperfusion injury","volume":"17","author":"Bei","year":"2019","journal-title":"BMC Med"},{"issue":"4","key":"10.1016\/j.ebiom.2022.104274_bib0023","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1161\/CIRCULATIONAHA.120.050446","article-title":"Long noncoding RNA cardiac physiological hypertrophy-associated regulator induces cardiac physiological hypertrophy and promotes functional recovery after myocardial ischemia-reperfusion injury","volume":"144","author":"Gao","year":"2021","journal-title":"Circulation"},{"issue":"2","key":"10.1016\/j.ebiom.2022.104274_bib0024","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1161\/CIRCRESAHA.119.315483","article-title":"Metabolic remodeling promotes cardiac hypertrophy by directing glucose to aspartate biosynthesis","volume":"126","author":"Ritterhoff","year":"2020","journal-title":"Circ Res"},{"issue":"4","key":"10.1016\/j.ebiom.2022.104274_bib0025","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1161\/HYPERTENSIONAHA.114.04806","article-title":"Novel role for caspase-activated DNase in the regulation of pathological cardiac hypertrophy","volume":"65","author":"Gao","year":"2015","journal-title":"Hypertension"},{"issue":"4","key":"10.1016\/j.ebiom.2022.104274_bib0026","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1161\/HYPERTENSIONAHA.113.02653","article-title":"Interferon regulatory factor 7 functions as a novel negative regulator of pathological cardiac hypertrophy","volume":"63","author":"Jiang","year":"2014","journal-title":"Hypertension"},{"issue":"10","key":"10.1016\/j.ebiom.2022.104274_bib0027","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1161\/CIRCRESAHA.115.306624","article-title":"miR-206 mediates yap-induced cardiac hypertrophy and survival","volume":"117","author":"Yang","year":"2015","journal-title":"Circ Res"},{"issue":"5","key":"10.1016\/j.ebiom.2022.104274_bib0028","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1161\/HYPERTENSIONAHA.121.17574","article-title":"Percutaneous intracoronary delivery of plasma extracellular vesicles protects the myocardium against ischemia-reperfusion injury in Canis","volume":"78","author":"Wang","year":"2021","journal-title":"Hypertension"},{"issue":"326","key":"10.1016\/j.ebiom.2022.104274_bib0029","doi-asserted-by":"crossref","first-page":"326ra22","DOI":"10.1126\/scitranslmed.aaf1475","article-title":"Long noncoding RNA Chast promotes cardiac remodeling","volume":"8","author":"Viereck","year":"2016","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.ebiom.2022.104274_bib0030","doi-asserted-by":"crossref","first-page":"15201","DOI":"10.1038\/ncomms15201","article-title":"miR-29b contributes to multiple types of muscle atrophy","volume":"8","author":"Li","year":"2017","journal-title":"Nat Commun"},{"issue":"1","key":"10.1016\/j.ebiom.2022.104274_bib0031","doi-asserted-by":"crossref","first-page":"11839","DOI":"10.1038\/s41598-021-91214-2","article-title":"Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction","volume":"11","author":"Luo","year":"2021","journal-title":"Sci Rep"},{"issue":"2","key":"10.1016\/j.ebiom.2022.104274_bib0032","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/jnr.23293","article-title":"The Erk MAP kinase pathway is activated at muscle spindles and is required for induction of the muscle spindle-specific gene Egr3 by neuregulin1","volume":"92","author":"Herndon","year":"2014","journal-title":"J Neurosci Res"},{"issue":"1","key":"10.1016\/j.ebiom.2022.104274_bib0033","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1038\/s41598-017-02585-4","article-title":"ANO1 inhibits cardiac fibrosis after myocardial infraction via TGF-beta\/smad3 pathway","volume":"7","author":"Gao","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"10.1016\/j.ebiom.2022.104274_bib0034","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1159\/000486771","article-title":"Hypoxia suppresses TGF-B1-induced cardiac myocyte myofibroblast transformation by inhibiting Smad2\/3 and Rhoa signaling pathways","volume":"45","author":"Yan","year":"2018","journal-title":"Cell Physiol Biochem"},{"issue":"1","key":"10.1016\/j.ebiom.2022.104274_bib0035","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/FJC.0000000000001292","article-title":"Knockdown of HIPK2 attenuates angiotensin II-induced cardiac fibrosis in cardiac fibroblasts","volume":"80","author":"Xu","year":"2022","journal-title":"J Cardiovasc Pharmacol"},{"issue":"6","key":"10.1016\/j.ebiom.2022.104274_bib0036","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.jshs.2020.11.009","article-title":"IGF1-PI3K-induced physiological cardiac hypertrophy: Implications for new heart failure therapies, biomarkers, and predicting cardiotoxicity","volume":"10","author":"Bass-Stringer","year":"2021","journal-title":"J Sport Health Sci"},{"issue":"23","key":"10.1016\/j.ebiom.2022.104274_bib0037","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1182\/blood-2009-07-235093","article-title":"Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation","volume":"115","author":"Hattangadi","year":"2010","journal-title":"Blood"},{"issue":"2","key":"10.1016\/j.ebiom.2022.104274_bib0038","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1161\/CIRCRESAHA.110.231514","article-title":"Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth","volume":"108","author":"Kehat","year":"2011","journal-title":"Circ Res"},{"issue":"7224","key":"10.1016\/j.ebiom.2022.104274_bib0039","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"},{"issue":"2","key":"10.1016\/j.ebiom.2022.104274_bib0040","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1083\/jcb.200406131","article-title":"Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival","volume":"167","author":"Wiggins","year":"2004","journal-title":"J Cell Biol"},{"issue":"17","key":"10.1016\/j.ebiom.2022.104274_bib0041","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1242\/dev.023960","article-title":"Abnormal sympathetic nervous system development and physiological dysautonomia in Egr3-deficient mice","volume":"135","author":"Eldredge","year":"2008","journal-title":"Development"},{"issue":"21","key":"10.1016\/j.ebiom.2022.104274_bib0042","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1038\/sj.onc.1210959","article-title":"The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis","volume":"27","author":"Liu","year":"2008","journal-title":"Oncogene"},{"issue":"6","key":"10.1016\/j.ebiom.2022.104274_bib0043","doi-asserted-by":"crossref","first-page":"H1592","DOI":"10.1152\/ajpheart.00337.2018","article-title":"Progression of myocardial ischemia leads to unique changes in immediate-early gene expression in the spinal cord dorsal horn","volume":"315","author":"Saddic","year":"2018","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"1","key":"10.1016\/j.ebiom.2022.104274_bib0044","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/jcmm.15814","article-title":"Cardiac fibroblast miR-27a may function as an endogenous anti-fibrotic by negatively regulating early growth response protein 3 (EGR3)","volume":"25","author":"Teng","year":"2021","journal-title":"J Cell Mol Med"},{"issue":"1","key":"10.1016\/j.ebiom.2022.104274_bib0045","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003747","article-title":"Early regulation of profibrotic genes in primary human cardiac myocytes by Trypanosoma cruzi","volume":"10","author":"Udoko","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"10.1016\/j.ebiom.2022.104274_bib0046","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.ajpath.2013.06.016","article-title":"Early growth response 3 (Egr-3) is induced by transforming growth factor-beta and regulates fibrogenic responses","volume":"183","author":"Fang","year":"2013","journal-title":"Am J Pathol"},{"issue":"14","key":"10.1016\/j.ebiom.2022.104274_bib0047","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1161\/CIRCULATIONAHA.116.022668","article-title":"Necrotic cell sensor Clec4e promotes a proatherogenic macrophage phenotype through activation of the unfolded protein response","volume":"134","author":"Clement","year":"2016","journal-title":"Circulation"},{"issue":"19","key":"10.1016\/j.ebiom.2022.104274_bib0048","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1161\/CIRCULATIONAHA.107.704197","article-title":"Essential role of Smad3 in infarct healing and in the pathogenesis of cardiac remodeling","volume":"116","author":"Bujak","year":"2007","journal-title":"Circulation"},{"issue":"7","key":"10.1016\/j.ebiom.2022.104274_bib0049","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1161\/CIRCULATIONAHA.117.029622","article-title":"Opposing actions of fibroblast and cardiomyocyte smad3 signaling in the infarcted myocardium","volume":"137","author":"Kong","year":"2018","journal-title":"Circulation"}],"container-title":["eBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S235239642200456X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S235239642200456X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T19:19:38Z","timestamp":1762456778000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S235239642200456X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":49,"alternative-id":["S235239642200456X"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2022.104274","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Inhibition of HIPK2 protects stress-induced pathological cardiac remodeling","name":"articletitle","label":"Article Title"},{"value":"eBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2022.104274","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"104274"}}