Mechano-regulated tenascin-C orchestrates muscle repair

Flück, Martin; Mund, Sonja I; Schittny, Johannes C; Klossner, Stephan; Durieux, Anne-Cécile; Giraud, Marie-Noëlle (2008). Mechano-regulated tenascin-C orchestrates muscle repair. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 105(36), pp. 13662-7. Washington, D.C.: National Academy of Sciences NAS 10.1073/pnas.0805365105

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Tenascin-C (TNC) is a mechano-regulated, morphogenic, extracellular matrix protein that is associated with tissue remodeling. The physiological role of TNC remains unclear because transgenic mice engineered for a TNC deficiency, via a defect in TNC secretion, show no major pathologies. We hypothesized that TNC-deficient mice would demonstrate defects in the repair of damaged leg muscles, which would be of functional significance because this tissue is subjected to frequent cycles of mechanical damage and regeneration. TNC-deficient mice demonstrated a blunted expression of the large TNC isoform and a selective atrophy of fast-muscle fibers associated with a defective, fast myogenic expression response to a damaging mechanical challenge. Transcript profiling mapped a set of de-adhesion, angiogenesis, and wound healing regulators as TNC expression targets in striated muscle. Expression of these regulators correlated with the residual expression of a damage-related 200-kDa protein, which resembled the small TNC isoform. Somatic knockin of TNC in fast-muscle fibers confirmed the activation of a complex expression program of interstitial and slow myofiber repair by myofiber-derived TNC. The results presented here show that a TNC-orchestrated molecular pathway integrates muscle repair into the load-dependent control of the striated muscle phenotype.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy 04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Heart Surgery
UniBE Contributor:	Flück, Martin, Mund, Sonja, Schittny, Johannes, Klossner, Stephan, Durieux, Anne Cécile, Giraud, Marie-Noelle
ISSN:	0027-8424
ISBN:	18757758
Publisher:	National Academy of Sciences NAS
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:03
Last Modified:	27 Feb 2024 14:29
Publisher DOI:	10.1073/pnas.0805365105
PubMed ID:	18757758
Web of Science ID:	000259251700086
URI:	https://boris.unibe.ch/id/eprint/27529 (FactScience: 108737)