Tenascin-C regulates recruitment of myofibroblasts during tissue repair after myocardial injury.
Tenascin-C (TN-C) is an extracellular matrix molecule that is expressed during wound healing in various tissues. Although not detectable in the normal adult heart, it is expressed under pathological conditions. Previously, using a rat model, we found that TN-C was expressed during the acute stage after myocardial infarction and that alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts appeared in TN-C-positive areas. In the present study, we examined whether TN-C controls the dynamics of myofibroblast recruitment and wound healing after electrical injury to the myocardium of TN-C knockout (TNKO) mice compared with wild-type (WT) mice. In TNKO mice, myocardial repair seemed to proceed normally, but the appearance of myofibroblasts was delayed. With cultured cardiac fibroblasts, TN-C significantly accelerated cell migration, alpha-SMA expression, and collagen gel contraction but did not affect proliferation. Using recombinant fragments of murine TN-C, the functional domain responsible for promoting migration of cardiac fibroblasts was mapped to the conserved fibronectin type III (FNIII)-like repeats and the fibrinogen (Fbg)-like domain. Furthermore, alternatively spliced FNIII and Fbg-like domains proved responsible for the up-regulation of alpha-SMA expression. These results indicate that TN-C promotes recruitment of myofibroblasts in the early stages of myocardial repair by stimulating cell migration and differentiation.
Department of Pathology and Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Masashi
M
Tamaoki
Kyoko
K
Imanaka-Yoshida
Kazuto
K
Yokoyama
Tomohiro
T
Nishioka
Hiroyasu
H
Inada
Michiaki
M
Hiroe
Teruyo
T
Sakakura
Toshimichi
T
Yoshida
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D005347:Fibroblasts; D006335:Heart Injuries / Q000473:pathology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
D011994:Recombinant Proteins; D019063:Tenascin