Department of Anatomy, Histology & Forensic Medicine, Section Histology, University of Florence, Florence, Italy.
J Cell Mol Med. 2012 Mar;16(3):507-19. doi: 10.1111/j.1582-4934.2011.01328.x.
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.
证明成年心脏含有心肌祖细胞，这些细胞可以被募集来替代受损的心肌，这激发了人们对能够改善这些细胞分化的新型分子的兴趣。在这种情况下，肽激素松弛素（RLX）最近被验证为心血管激素，是一个有前途的候选者。本研究旨在测试 RLX 是否可能促进原代培养的新生小鼠未成熟心肌细胞的生长和成熟的假说。通过结合分子生物学、形态学和电生理学，在添加人重组 H2 RLX（100ng/ml）或普通培养基后 2、12、24 和 48 小时，对培养物进行了研究。RLX 调节细胞增殖，在 2 和 12 小时促进增殖，在 24 小时抑制增殖；RLX 还在 mRNA 和蛋白质水平上诱导了两种心脏特异性转录因子（GATA-4 和 Nkx2-5）和心脏特异性结构基因（连接蛋白 43、肌钙蛋白 T 和 HCN4 离子通道）的表达。一致地，RLX 诱导出现功能成熟的心肌细胞的超微结构和电生理特征。总之，本研究提供了新的间接证据，表明 RLX 通过促进未成熟心肌细胞的增殖和成熟来特异性作用于它们。这一概念表明，RLX 作为心脏既是来源又是靶器官的物质，可能是产前心脏形态发生的内源性调节剂，并可能作为内源性心肌源性因子和外源性心脏趋向性药物参与成年期的心脏再生和修复。
