کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8715859 1587873 2018 32 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
β-Adrenergic Receptor Trafficking, Degradation, and Cell Surface Expression Are Altered in Dermal Fibroblasts from Hypertrophic Scars
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
β-Adrenergic Receptor Trafficking, Degradation, and Cell Surface Expression Are Altered in Dermal Fibroblasts from Hypertrophic Scars
چکیده انگلیسی
Burn trauma elevates catecholamines for up to 2 years and causes hypertrophic scarring. Propranolol, a nonspecific β1-, β2-adrenergic receptor (AR) inverse agonist, counters the hypermetabolic response to elevated catecholamines and may decrease hypertrophic scarring by an unknown mechanism. We investigated the effect of burn injury on β1-, β2-, and β3-AR expression, trafficking, and degradation in human dermal fibroblasts from hypertrophic scar [HSF], non-scar fibroblasts, and normal fibroblasts. We also investigated the modulation of these events by propranolol. Catecholamine-stimulated cAMP production was lower in HSFs and non-scar fibroblasts than in normal fibroblasts. β1- and β2-AR cell surface expression was lowest in HSFs, but propranolol increased cell surface expression of these receptors. Basal β2-AR ubiquitination was higher in HSFs than non-scar or normal fibroblasts, suggesting accelerated receptor degradation. β-AR degradation was mainly driven by lysosomal-specific polyubiquitination at Lys-63 in normal fibroblasts and HSFs, which was abrogated by propranolol. Propranolol also targeted β-AR to the proteasome in HSFs. Confocal imaging showed a lack of β2-AR-GFP trafficking to lysosomal compartments in catecholamine-stimulated HSFs. These data suggest that burn trauma alters the expression, trafficking, and degradation of β-ARs in dermal fibroblasts, which may then affect fibroblast responses to propranolol.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 7, July 2018, Pages 1645-1655
نویسندگان
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