title: Relaxin promotes growth and maturation of mouse neonatal cardiomyocytes in vitro: clues for cardiac regeneration.
abstract: The demonstration that the adult heart contains myocardial progenitor cells which can be recruited in an attempt to replace the injured myocardium has sparkled interest towards novel molecules capable of improving the differentiation of these cells. In this context, the peptide hormone relaxin (RLX), recently validated as a cardiovascular hormone, is a promising candidate. This study was designed to test the hypothesis that RLX may promote the growth and maturation of mouse neonatal immature cardiomyocytes in primary culture. The cultures were studied at 2, 12, 24 and 48 hrs after the addition of human recombinant H2 RLX (100 ng/ml), the main circulating form of the hormone, or plain medium by combining molecular biology, morphology and electrophysiology. RLX modulated cell proliferation, promoting it at 2 and 12 hrs and inhibiting it at 24 hrs; RLX also induced the expression of both cardiac-specific transcription factors (GATA-4 and Nkx2-5) and cardiac-specific structural genes (connexin 43, troponin T and HCN4 ion channel) at both the mRNA and protein level. Consistently, RLX induced the appearance of ultrastructural and electrophysiological signs of functionally competent, mature cardiomyocytes. In conclusion, this study provides novel circumstantial evidence that RLX specifically acts on immature cardiomyocytes by promoting their proliferation and maturation. This notion suggests that RLX, for which the heart is both a source and target organ, may be an endogenous regulator of cardiac morphogenesis during pre-natal life and could participate in heart regeneration and repair, both as endogenous myocardium-derived factor and exogenous cardiotropic drug, during adult life.
authors.affiliation: Department of Anatomy, Histology & Forensic Medicine, Section Histology, University of Florence, Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nistri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
authors.forename: Chiara
authors.initials: C
authors.lastname: Sassoli
authors.forename: Roberta
authors.initials: R
authors.lastname: Squecco
authors.forename: Fabio
authors.initials: F
authors.lastname: Francini
authors.forename: Lucia
authors.initials: L
authors.lastname: Formigli
authors.forename: Daniele
authors.initials: D
authors.lastname: Bani
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000502:physiology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D012038:Regeneration; D012065:Relaxin / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020107:Troponin T / Q000235:genetics / Q000378:metabolism
chemical_list: D018031:Connexin 43; D054815:Cyclic Nucleotide-Gated Cation Channels; D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; C484469:Nkx2-5 protein, mouse; C095068:RLN2 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D020107:Troponin T; D012065:Relaxin