Zhang, Chen, Tan, Chek Kun, McFarlane, Craig, Sharma, Mridula, Tan, Nguan Soon, and Kambadur, Ravi (2012) Myostatin-null mice exhibit delayed skin wound healing through the blockade of transforming growth factor-β signaling by decorin. American Journal of Physiology: cell physiology, 302. C1213-C1225.

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Abstract

Myostatin (Mstn) is a secreted growth and differentiation factor that belongs to the transforming growth factor-β (TGF-β) superfamily. Mstn has been well characterized as a regulator of myogenesis and has been shown to play a critical role in postnatal muscle regeneration. Herein, we report for the first time that Mstn is expressed in both epidermis and dermis of murine and human skin and that Mstn-null mice exhibited delayed skin wound healing attributable to a combination of effects resulting from delayed epidermal reepithelialization and dermal contraction. In epidermis, reduced keratinocyte migration and protracted keratinocyte proliferation were observed, which subsequently led to delayed recovery of epidermal thickness and slower reepithelialization. Furthermore, primary keratinocytes derived from Mstn-null mice displayed reduced migration capacity and increased proliferation rate as assessed through in vitro migration and adhesion assays, as well as bromodeoxyuridine incorporation and Western blot analysis. Moreover, in dermis, both fibroblast-to-myofibroblast transformation and collagen deposition were concomitantly reduced, resulting in a delayed dermal wound contraction. These decreases are due to the inhibition of TGF-β signaling. In agreement, the expression of decorin, a naturally occurring TGF-β suppressor, was elevated in Mstn-null mice; moreover, topical treatment with TGF-β1 protein rescued the impaired skin wound healing observed in Mstn-null mice. These observations highlight the interplay between TGF-β and Mstn signaling pathways, specifically through Mstn regulation of decorin levels during the skin wound healing process. Thus we propose that Mstn agonists might be beneficial for skin wound repair.

Item ID:	52336
Item Type:	Article (Research - C1)
ISSN:	1522-1563
Funders:	Nanyang Technical University
Date Deposited:	23 Feb 2018 05:58
FoR Codes:	06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 60% 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060106 Cellular Interactions (incl Adhesion, Matrix, Cell Wall) @ 40%
SEO Codes:	97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 40% 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 30% 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920117 Skin and Related Disorders @ 30%
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