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 language | English (US) |
|---|---|
| Journal | Journal of Investigative Dermatology |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Dermatology
- Cell Biology
Cite this
β-Adrenergic Receptor Trafficking, Degradation, and Cell Surface Expression Are Altered in Dermal Fibroblasts from Hypertrophic Scars. / El Ayadi, Amina; Prasai, Anesh; Wang, Ye; Herndon, David; Finnerty, Celeste.
In: Journal of Investigative Dermatology, 01.01.2018.Research output: Contribution to journal › Article
}
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.
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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
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
ER -