TY - JOUR
T1 - Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair
AU - Li, Haichang
AU - Duann, Pu
AU - Lin, Pei Hui
AU - Zhao, Li
AU - Fan, Zhaobo
AU - Tan, Tao
AU - Zhou, Xinyu
AU - Sun, Mingzhai
AU - Fu, Minghuan
AU - Orange, Matthew
AU - Sermersheim, Matthew
AU - Ma, Hanley
AU - He, Duofen
AU - Steinberg, Steven M.
AU - Higgins, Robert
AU - Zhu, Hua
AU - John, Elizabeth
AU - Zeng, Chunyu
AU - Guan, Jianjun
AU - Ma, Jianjie
N1 - Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2015/10/2
Y1 - 2015/10/2
N2 - Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53-/- mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing.
AB - Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53-/- mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing.
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U2 - 10.1074/jbc.M115.680074
DO - 10.1074/jbc.M115.680074
M3 - Article
C2 - 26306047
AN - SCOPUS:84943311583
SN - 0021-9258
VL - 290
SP - 24592
EP - 24603
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -