title: Regulation of connective tissue remodeling in the early phase of denervation in a rat skeletal muscle.
abstract: Denervation alters the metabolism of the extracellular matrix (ECM) in skeletal muscle; however, the underlying mechanisms of ECM remodeling are not fully understood. The aim of this study was to elucidate the dynamic features of the ECM regulatory process in the early phase of denervated skeletal muscle in male Wistar rats. We investigated the expression of collagens (total, type I, and type III), transforming growth factor beta 1 (TGF-β1), and matrix metalloproteases (MMPs) together with their endogenous inhibitors (TIMPs), at the mRNA and/or protein level in the soleus muscles of control animals and at days 3, 7, and 14 post-denervation. Expression of mRNA encoding collagens was decreased at days 3 and 7, and had recovered by day 14, in parallel with total collagen protein content. Content of TGF-β1 protein was elevated sequentially, up to a maximum of 158% at day 14 post-denervation (P < 0.05), as was TIMP-2 mRNA expression (272% at day 14), whereas MMP-1, MMP-2, and TIMP-1 mRNA expression was not affected at any stage. The initial reduction of collagen mRNA may be responsible for hypoactivity caused by the disappearance of contractile function. Recovery of collagen mRNA/protein at day 14 may be due mainly to the suppressive effects of TGF-β1 on collagen degradation via TIMP-2 upregulation.
authors.affiliation: Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Higashi-Hiroshima, Hiroshima, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ozawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kurose
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kawamata
authors.forename: Akinori
authors.initials: A
authors.lastname: Kaneguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kito
mesh_terms: D000818:Animals; D001835:Body Weight; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D003238:Connective Tissue / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1