کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9230119 1203611 2005 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Endothelial Protein C Receptor and Protease-Activated Receptor-1 Mediate Induction of a Wound-Healing Phenotype in Human Keratinocytes by Activated Protein C
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
Endothelial Protein C Receptor and Protease-Activated Receptor-1 Mediate Induction of a Wound-Healing Phenotype in Human Keratinocytes by Activated Protein C
چکیده انگلیسی
Activated protein C (APC) is a natural anticoagulant and inhibitor of inflammation that can stimulate keratinocyte wound repair in vitro and promote wound healing in vivo. The signaling mechanisms, however, are unknown and a keratinocyte receptor for APC has not been identified. Here, we show that cultured human keratinocytes from neonatal foreskins express the endothelial protein C receptor (EPCR). EPCR was also strongly expressed by lower epidermal layers of neonatal foreskin as determined by immunohistochemistry. In cultured keratinocytes, EPCR expression was upregulated by the addition of APC and inhibited by tumor necrosis factor-α. Addition of APC stimulated cell proliferation, production of matrix metalloproteinase-2, activation of ERK and p38 kinase signaling pathways, and expression of protease-activated receptor (PAR)-1. A monoclonal antibody, RCR252, which blocks APC binding to EPCR, or a blocking antibody to PAR-1, abolished APC's effects on keratinocytes. In summary, this study demonstrates that EPCR, a major receptor of protein C pathway, is expressed by human keratinocytes, and facilitates APC's function on keratinocytes via activation of PAR-1 pathway. Our findings highlight a possible new role for the protein C pathway in skin physiology and help elucidate the mechanisms of action by which APC promotes wound healing.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 125, Issue 6, December 2005, Pages 1279-1285
نویسندگان
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