Regulation of connexin gene expression during skeletal muscle regeneration in the adult rat

• Published in: American Journal of Physiology: Cell Physiology 2009-03, Vol.296 (3), p.C593-C606
• Main Authors: Trovato-Salinaro, A, Belluardo, N, Frinchi, M, von Maltzahn, J, Willecke, K, Condorelli, D. F, Mudo, G
• Format: Article
• Language: English
• Subjects: Animals; Cell Aggregation; Cell Fusion; Cell Proliferation; Cells; Connexin 30; Connexin 43 - metabolism; Connexins - genetics; Connexins - metabolism; Constriction; Endothelial Cells - metabolism; Gap Junction alpha-4 Protein; Gap Junction alpha-5 Protein; Gene expression; Gene Expression Regulation; Genes; Immunohistochemistry; In Situ Hybridization; Male; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal - surgery; Musculoskeletal system; Neovascularization, Physiologic; Rats; Rats, Wistar; Regeneration - genetics; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Time Factors
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00458.2008

1 Department of Experimental Medicine, Section of Human Physiology, Laboratory of Neurobiology, University of Palermo, Palermo, Italy; 2 Department of Chemical Science, Section of Biochemistry and Molecular Biology, University of Catania, Catania, Italy; and 3 Institute of Genetics, Division of Molecular Genetics, University of Bonn, Bonn, Germany Submitted 7 September 2008 ; accepted in final form 2 January 2009 In the adult skeletal muscle, various kinds of trauma promote proliferation of satellite cells that differentiate into myoblasts forming new myofibers or to repair the damaged one. The aim of present work was to perform a comparative spatial and temporal analysis of connexin (Cx) 37, Cx39, Cx40, Cx43, and Cx45 expression in the adult regenerating skeletal muscle in response to crush injury. Within 24 h from injury, Cx37 expression was upregulated in the endothelial cells of blood vessels, and, 5 days after injury, Cx37-expressing cells were found inside the area of lesion and formed clusters generating new blood vessels with endothelial cells expressing Cx37. Three days after injury, Cx39 mRNA was selectively expressed in myogenin-positive cells, forming rows of closely apposed cell nuclei fusing in myotubes. Cx40 mRNA-labeled cells were observed within 24 h from injury in the endothelium of blood vessels, and, 5 days after lesion, Cx40-labeled cells were found inside the area of lesion-forming rows of myogenin-positive, closely apposed cells coexpressing Cx39. Within 24 h from lesion, both Cx43 and Cx45 mRNAs were upregulated in individual cells, and some of them were positive for M-cadherin. Three days after injury, a large number of both Cx43 and Cx45 mRNA-labeled and myogenin-positive cells were found inside the area of lesion. Taken together, these results show that at least four Cxs, out of five expressed in regenerating skeletal muscle, can be differentially involved in communication of myogenic cells during the process of cell proliferation, aggregation, and fusion to form new myotubes or to repair damaged myofibers. connexin 37; connexin 39; connexin 40; connexin 43; connexin 45; myogenic cells; muscle regeneration Address for reprint requests and other correspondence: Giuseppa Mudò, Dept. of Experimental Medicine, Section of Human Physiology, Univ. of Palermo, corso Tukory 129, 90134 Palermo, Italy (e-mail: g.mudo{at}unipa.it )