Plastic Surgery Research Council
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FIBROMODULIN INDUCES ANGIOGENESIS DURING CUTANEOUS WOUND HEALING
Presenter: Zhong Zheng, MD
Co-Authors: Jian J; Zheng Z; Hsu CY; Velasco O; Zhang K; Wang J; Zhang X; Ting K; Soo C
University of California Los Angeles

Fibromodulin (FMOD) is a 59 kD extracellular matrix (ECM) proteoglycan shown to have critical roles in collagen fibrillogenesis, transforming growth factor (TGF≤)-? modulation, scarless fetal skin repair, and stromal cell reprogramming. Our previous studies demonstrated that exogenous FMOD significantly reduced adult scar formation, improved collagen architecture, and increased wound tensile strength. In FMOD-null mouse wounds, granulation tissue formation was minimal with less blood vessel formation than the wild type (WT). In this study, exogenous FMOD administration significantly increased capillary density in both FMOD-null and WT adult mouse and adult rat cutaneous wounds. In support of this, FMOD treated wounds exhibited marked upregulation of angiogenesis related genes such as vascular endothelial growth factor (VEGF), angiopoietin 1 (ANGPT1), fibroblast growth factor (FGF-2), and platelet-derived growth factor-A (PDGF-A). To further confirm FMOD s role in promoting angiogenesis we performed various in vitro and in vivo assays, First, FMOD promoted human primary umbilical vein endothelial cells (HUVECs) in vitro to increase tube length, junction, branch and mesh formation in a dose-dependent manner. Second, FMOD robustly increased blood vessel formation on the chorioallantoic membrane of chicken embryos (CAM). Third, FMOD induced significant cell migration and capillary formation into Matrigel plugs implanted in vivo. In summary, we demonstrate an additional novel pro-angiogenic quality of FMOD for optimal wound repair . Clinically, FMOD may promote cutaneous healing in poorly vascularized wounds such as diabetic or irradiated wounds.


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