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Tenotomy immobilization as a model to investigate skeletal muscle fibrosis with emphasis on Secreted frizzled related protein 2      
Yazarlar
Dr. Öğr. Üyesi Uğur AKPULAT
Kastamonu Üniversitesi, Türkiye
İlyas Onbaşılar
Hacettepe Üniversitesi, Türkiye
Yusuf Çetin Kocaefe
Hacettepe Üniversitesi, Türkiye
Özet
The pathological endpoint of congenital and senile myopathies is chronic muscle degeneration characterized by the atrophy of contractile elements, accompanied by fibrosis and fatty infiltration of the interstitium. Tenotomy is the release of preload that causes abrupt shortening of the muscle and models atrophy and fibrosis without prominent inflammatory response. Fibrosis in the skeletal muscle is known to be triggered by transforming growth factor (TGF)-β, which is activated by inflammatory events. As these were lacking, tenotomy provided an opportunity to investigate transcriptional events on a background without inflammation. An unbiased look at the transcriptome of tenotomyimmobilized soleus muscle revealed that the majority of the transcriptional changes took place in the first 4 wk. Regarding atrophy, proteasomal and lysosomal pathways were actively involved in accompanying cathepsins and calpains in the breakdown of the macromolecular contractile machinery. The transcriptome provided clearcut evidence for the upregulation of collagens and several extracellular matrix components that define fibrotic remodeling of the skeletal muscle architecture as well as activation of the fibro-adipogenic precursors. Concomitantly, Sfrp2, a Wnt antagonist as well as a procollagen processor, accompanied fibrosis in skeletal muscle with an expression that was stringently confined to the slow-twitch fibers. An interpreted mechanistic scenario construed the kinetic events initiated through the abnormal shortening of the muscle fibers as enough to trigger the resident latent TGF-β in the extracellular matrix, leading to the activation of fibroadipogenic precursors. As in the heart, Sfrp2 shows itself to be a therapeutic target for the prevention of irreversible fibrosis in degenerative skeletal muscle conditions.
Anahtar Kelimeler
Fibrosis | Immobilization | Muscle atrophy | Sfrp2 | Tenotomy
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı Physiological Genomics
Dergi ISSN 1094-8341
Dergi Tarandığı Indeksler SCI
Makale Dili İngilizce
Basım Tarihi 06-2016
Cilt No 48
Sayı 6
Sayfalar 397 / 408
Doi Numarası 10.1152/physiolgenomics.00010.2016
Makale Linki http://physiolgenomics.physiology.org/lookup/doi/10.1152/physiolgenomics.00010.2016