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 af...

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Veröffentlicht in:The American journal of pathology 2005-07, Vol.167 (1), p.71-80
Hauptverfasser: Tamaoki, Masashi, Imanaka-Yoshida, Kyoko, Yokoyama, Kazuto, Nishioka, Tomohiro, Inada, Hiroyasu, Hiroe, Michiaki, Sakakura, Teruyo, Yoshida, Toshimichi
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Sprache:eng
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Zusammenfassung: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 α-smooth muscle actin (α-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, α-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 α-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.
ISSN:0002-9440
1525-2191
DOI:10.1016/S0002-9440(10)62954-9