Mechano-regulated Tenascin-C orchestrates muscle repair

Abstract

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 damagerelated 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.damage ͉ expression ͉ extracellular ͉ gene therapy ͉ myogenesis

Impaired border zone formation and adverse remodeling after reperfused myocardial infarction in cannabinoid CB2 receptor deficient mice

“…Thrombospondin-1 has been associated with the demarcation of infarction and its deficiency was also associated with uncontrolled expansion of infarction size [5,24]. Our study also showed a CB2 receptor-dependent induction of tenascin C expression, an early marker of tissue remodeling and repair [25]. Based on scar morphology in Cnr2 −/− mice we postulate, that the expression of collagen subtypes and their cross-linking enzyme lysyl oxidase seems to be at least partially influenced by CB2 receptor, as we already suggested before [10].…”

Mechano-transduction to muscle protein synthesis is modulated by FAK

“…Electronique et Informatique du Pilat, Jonzieux, France). This technique allows to maintain the overexpression for more than 1 week (Fluck et al 2008). Typically, mice recovered rapidly from this procedure and began to move freely 2 h after the intervention.…”

Responses of muscle mass, strength and gene transcripts to long-term heat stress in healthy human subjects

“…Long-term heat stress-induced transcript was evaluated using Significance Analysis of Microarray (SAM) at locally determined false discovery rate (Däpp et al 2004;Flück et al 2008;Schmutz et al 2010;Tusher et al 2001). For each of the genes (gene probes) on the DNA microiarray, differential gene expression was considered significant when the effective false discovery rate (q-value) was below the lowest false discovery rate as calculated by permutations of gene-specific test in SAM.…”