Franklin Chu - Academia.edu (original) (raw)
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National University of Singapore
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Papers by Franklin Chu
Journal of Investigative Dermatology, 2011
Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair... more Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair through, in part, transforming growth factor-b (TGF-b) modulation. Using an adult fmod-null (fmod À/À ) mouse model, this study further elucidates the interplay between FMOD and TGF-b expression during cutaneous repair and scar formation. Full-thickness skin wounds on fmod À/À 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 À/À mice relative to WT, which was partially rescued by exogenous FMOD administration. In addition, fmod À/À wounds exhibited early elevation (within 24 hours post-wounding) of type I and type II TGF-b receptors as well as unexpectedly high fibroblast expression of TGF-b3, a molecule with reported antifibrotic and antimigratory effects. Consistent with elevated fibroblastic TGF-b3, fmod À/À fibroblasts were significantly less motile than WT fibroblasts. fmod À/À fibroblasts were also more susceptible to migration inhibition by TGF-b3, leading to profound delays in dermal cell migration. Increased scarring in fmod À/À mice indicates that TGF-b3's antimotility effects predominate over its antifibrotic effects when high TGF-b3 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-b bioactivity.
Journal of Investigative Dermatology, 2011
Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair... more Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair through, in part, transforming growth factor-b (TGF-b) modulation. Using an adult fmod-null (fmod À/À ) mouse model, this study further elucidates the interplay between FMOD and TGF-b expression during cutaneous repair and scar formation. Full-thickness skin wounds on fmod À/À 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 À/À mice relative to WT, which was partially rescued by exogenous FMOD administration. In addition, fmod À/À wounds exhibited early elevation (within 24 hours post-wounding) of type I and type II TGF-b receptors as well as unexpectedly high fibroblast expression of TGF-b3, a molecule with reported antifibrotic and antimigratory effects. Consistent with elevated fibroblastic TGF-b3, fmod À/À fibroblasts were significantly less motile than WT fibroblasts. fmod À/À fibroblasts were also more susceptible to migration inhibition by TGF-b3, leading to profound delays in dermal cell migration. Increased scarring in fmod À/À mice indicates that TGF-b3's antimotility effects predominate over its antifibrotic effects when high TGF-b3 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-b bioactivity.