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Delayed wound closure in fibromodulin-deficient mice is associated with increased TGF-?3 signaling.


ABSTRACT: Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair through, in part, transforming growth factor-? (TGF-?) modulation. Using an adult fmod-null (fmod(-/-)) mouse model, this study further elucidates the interplay between FMOD and TGF-? expression during cutaneous repair and scar formation. Full-thickness skin wounds on fmod(-/-) and wild-type (WT) mice were closed primarily and analyzed. Histomorphometry revealed delayed dermal cell migration leading to delayed wound closure and significantly increased scar size in fmod(-/-) mice relative to WT, which was partially rescued by exogenous FMOD administration. In addition, fmod(-/-) wounds exhibited early elevation (within 24? hours post-wounding) of type I and type II TGF-? receptors as well as unexpectedly high fibroblast expression of TGF-?3, a molecule with reported antifibrotic and antimigratory effects. Consistent with elevated fibroblastic TGF-?3, fmod(-/-) fibroblasts were significantly less motile than WT fibroblasts. fmod(-/-) fibroblasts were also more susceptible to migration inhibition by TGF-?3, leading to profound delays in dermal cell migration. Increased scarring in fmod(-/-) mice indicates that TGF-?3's antimotility effects predominate over its antifibrotic effects when high TGF-?3 levels disrupt early fibroblastic wound ingress. These studies demonstrate that FMOD presence is critical for proper temporospatial coordination of wound healing events and normal TGF-? bioactivity.

SUBMITTER: Zheng Z 

PROVIDER: S-EPMC4073663 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Delayed wound closure in fibromodulin-deficient mice is associated with increased TGF-β3 signaling.

Zheng Zhong Z   Nguyen Calvin C   Zhang Xinli X   Khorasani Hooman H   Wang Joyce Z JZ   Zara Janette N JN   Chu Franklin F   Yin Wei W   Pang Shen S   Le Anh A   Ting Kang K   Soo Chia C  

The Journal of investigative dermatology 20101230 3


Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair through, in part, transforming growth factor-β (TGF-β) modulation. Using an adult fmod-null (fmod(-/-)) mouse model, this study further elucidates the interplay between FMOD and TGF-β expression during cutaneous repair and scar formation. Full-thickness skin wounds on fmod(-/-) and wild-type (WT) mice were closed primarily and analyzed. Histomorphometry revealed delayed dermal cell migration leading  ...[more]

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