β-Adrenergic Receptor Trafficking, Degradation, and Cell Surface Expression Are Altered in Dermal Fibroblasts from Hypertrophic Scars

The Journal of Investigative Dermatology
Amina El AyadiCeleste C Finnerty

Abstract

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 catecholami...Continue Reading

Citations

Jul 25, 2018·Stem Cells and Development·Brice MagneMarina Trouillas
Jun 7, 2020·Cells·Jake J WenRavi S Radhakrishnan
Feb 13, 2020·International Journal of Molecular Sciences·Amina El AyadiAnesh Prasai
Dec 7, 2020·Burns : Journal of the International Society for Burn Injuries·Chaoyi ZhongJun Yao
Nov 24, 2020·The Journal of Investigative Dermatology·Roberto MaglieMichael Hertl

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