{"doi":"10.1172/jci135859","title":"p38 Mitogen-activated protein kinase regulates chamber-specific perinatal growth in heart","abstract":"In the mammalian heart, the left ventricle (LV) rapidly becomes more dominant in size and function over the right ventricle (RV) after birth. The molecular regulators responsible for this chamber-specific differential growth are largely unknown. We found that cardiomyocytes in the neonatal mouse RV had lower proliferation, more apoptosis, and a smaller average size compared with the LV. This chamber-specific growth pattern was associated with a selective activation of p38 mitogen-activated protein kinase (MAPK) activity in the RV and simultaneous inactivation in the LV. Cardiomyocyte-specific deletion of both the Mapk14 and Mapk11 genes in mice resulted in loss of p38 MAPK expression and activity in the neonatal heart. Inactivation of p38 activity led to a marked increase in cardiomyocyte proliferation and hypertrophy but diminished cardiomyocyte apoptosis, specifically in the RV. Consequently, the p38-inactivated hearts showed RV-specific enlargement postnatally, progressing to pulmonary hypertension and right heart failure at the adult stage. Chamber-specific p38 activity was associated with differential expression of dual-specific phosphatases (DUSPs) in neonatal hearts, including DUSP26. Unbiased transcriptome analysis revealed that IRE1α/XBP1-mediated gene regulation contributed to p38 MAPK-dependent regulation of neonatal cardiomyocyte proliferation and binucleation. These findings establish an obligatory role of DUSP/p38/IRE1α signaling in cardiomyocytes for chamber-specific growth in the postnatal heart.","journal":"Journal of Clinical Investigation","year":2020,"id":97861,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320461,"name":"Jin Li","orcid":"0000-0001-8652-8612","position":1,"is_corresponding":false},{"id":483428,"name":"Jijun Huang","orcid":"0000-0002-5520-193X","position":2,"is_corresponding":false},{"id":484082,"name":"Zhaojun Xiong","orcid":null,"position":3,"is_corresponding":false},{"id":483429,"name":"Qing Zhang","orcid":"0009-0005-5408-5286","position":4,"is_corresponding":false},{"id":98562,"name":"Tracey W. Chan","orcid":"0000-0002-1236-6304","position":5,"is_corresponding":false},{"id":385040,"name":"Yichen Ding","orcid":"0000-0002-6242-3506","position":6,"is_corresponding":false},{"id":428003,"name":"Christoph Rau","orcid":"0000-0002-0782-207X","position":7,"is_corresponding":false},{"id":484083,"name":"Kevin Sung","orcid":null,"position":8,"is_corresponding":false},{"id":244614,"name":"Shuxun Ren","orcid":"0000-0001-9208-3779","position":9,"is_corresponding":false},{"id":483430,"name":"Rajan P. Kulkarni","orcid":"0000-0002-2191-4085","position":10,"is_corresponding":false},{"id":385049,"name":"Tzung K. Hsiai","orcid":"0000-0003-1734-0792","position":11,"is_corresponding":false},{"id":43211,"name":"Xinshu Xiao","orcid":"0000-0002-9362-8029","position":12,"is_corresponding":false},{"id":329009,"name":"Marlin Touma","orcid":"0000-0002-2827-4068","position":13,"is_corresponding":false},{"id":483431,"name":"Susumu Minamisawa","orcid":"0000-0003-4728-2116","position":14,"is_corresponding":false},{"id":70763,"name":"Yibin Wang","orcid":"0000-0003-0852-0767","position":15,"is_corresponding":false},{"id":244612,"name":"Tomohiro Yokota","orcid":"0000-0003-2540-3810","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T22:36:02.818637Z","pmid":"32573492","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}