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

Amina El Ayadi, Anesh Prasai, Ye Wang, David Herndon, Celeste Finnerty

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 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.

Original languageEnglish (US)
JournalJournal of Investigative Dermatology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Hypertrophic Cicatrix
Fibroblasts
Adrenergic Receptors
Propranolol
Degradation
Skin
Catecholamines
Cicatrix
Wounds and Injuries
Adrenergic Agonists
Ubiquitination
Cell Surface Receptors
Proteasome Endopeptidase Complex
Modulation
Imaging techniques

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

@article{a92bd6f584c04cfc91a10639ce9d5547,
title = "β-Adrenergic Receptor Trafficking, Degradation, and Cell Surface Expression Are Altered in Dermal Fibroblasts from Hypertrophic Scars",
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 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.",
author = "{El Ayadi}, Amina and Anesh Prasai and Ye Wang and David Herndon and Celeste Finnerty",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.jid.2018.01.037",
language = "English (US)",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - β-Adrenergic Receptor Trafficking, Degradation, and Cell Surface Expression Are Altered in Dermal Fibroblasts from Hypertrophic Scars

AU - El Ayadi, Amina

AU - Prasai, Anesh

AU - Wang, Ye

AU - Herndon, David

AU - Finnerty, Celeste

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85046137253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046137253&partnerID=8YFLogxK

U2 - 10.1016/j.jid.2018.01.037

DO - 10.1016/j.jid.2018.01.037

M3 - Article

C2 - 29476776

AN - SCOPUS:85046137253

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

ER -