title: Acute inflammation stimulates a regenerative response in the neonatal mouse heart.
abstract: Cardiac injury in neonatal 1-day-old mice stimulates a regenerative response characterized by reactive cardiomyocyte proliferation, which is distinguished from the fibrotic repair process in adults. Acute inflammation occurs immediately after heart injury and has generally been believed to exert a negative effect on heart regeneration by promoting scar formation in adults; however, little is known about the role of acute inflammation in the cardiac regenerative response in neonatal mice. Here, we show that acute inflammation induced cardiomyocyte proliferation after apical intramyocardial microinjection of immunogenic zymosan A particles into the neonatal mouse heart. We also found that cardiac injury-induced regenerative response was suspended after immunosuppression in neonatal mice, and that cardiomyocytes could not be reactivated to proliferate after neonatal heart injury in the absence of interleukin-6 (IL-6). Furthermore, cardiomyocyte-specific deletion of signal transducer and activator of transcription 3 (STAT3), the major downstream effector of IL-6 signaling, decreased reactive cardiomyocyte proliferation after apical resection. Our results indicate that acute inflammation stimulates the regenerative response in neonatal mouse heart, and suggest that modulation of inflammatory signals might have important implications in cardiac regenerative medicine.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Chunyong
authors.initials: C
authors.lastname: Han
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lian
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Shengshou
authors.initials: S
authors.lastname: Hu
mesh_terms: D000208:Acute Disease; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D006321:Heart / Q000254:growth & development / Q000502:physiology* / Q000503:physiopathology; D006335:Heart Injuries / Q000276:immunology* / Q000503:physiopathology; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000276:immunology; D012038:Regeneration; D050796:STAT3 Transcription Factor / Q000276:immunology; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor