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

Amina El Ayadi1, Anesh Prasai1, Ye Wang1

  • 1Department of Surgery, University of Texas Medical Branch, Galveston, Texas, USA; Shriners Hospitals for Children-Galveston, Galveston, Texas, USA.

The Journal of Investigative Dermatology
|February 25, 2018
PubMed

Insights

Burn trauma alters adrenergic receptor (AR) expression and trafficking in skin fibroblasts. Propranolol may improve hypertrophic scarring by modulating these altered AR pathways.

Area of Science:

  • Cellular and Molecular Biology
  • Dermatology
  • Pharmacology

Background:

  • Burn trauma causes prolonged elevation of catecholamines, potentially leading to hypertrophic scarring.
  • Propranolol, a beta-adrenergic receptor (AR) inverse agonist, may mitigate hypertrophic scarring via unknown mechanisms.
  • Understanding AR regulation in fibroblasts is crucial for developing effective burn scar treatments.

Purpose of the Study:

  • To investigate the impact of burn injury on beta-1, beta-2, and beta-3 AR expression, trafficking, and degradation in human dermal fibroblasts.
  • To examine how propranolol modulates these AR-related processes in fibroblasts from normal skin, non-scar areas, and hypertrophic scars.
  • To elucidate the role of AR signaling in the development of hypertrophic scarring post-burn.

Main Methods:

  • Comparison of catecholamine-stimulated cAMP production in normal, non-scar, and hypertrophic scar fibroblasts (HSFs).
  • Assessment of beta-1 and beta-2 AR cell surface expression and basal beta-2 AR ubiquitination in different fibroblast types.
  • Analysis of beta-AR degradation pathways (lysosomal vs. proteasomal) and receptor trafficking using confocal imaging and propranolol treatment.

Main Results:

  • Catecholamine-stimulated cAMP production was reduced in HSFs and non-scar fibroblasts compared to normal fibroblasts.
  • HSFs exhibited lower basal cell surface expression of beta-1 and beta-2 ARs, which propranolol treatment increased.
  • Propranolol abrogated lysosomal degradation of beta-ARs and promoted proteasomal targeting in HSFs, while HSFs showed impaired beta-2-AR trafficking to lysosomes.

Conclusions:

  • Burn trauma significantly alters beta-adrenergic receptor expression, ubiquitination, and degradation in dermal fibroblasts.
  • Propranolol influences beta-AR trafficking and degradation pathways, suggesting a potential mechanism for its therapeutic effect on hypertrophic scarring.
  • These findings highlight the dysregulation of beta-AR signaling in hypertrophic scarring and offer insights into propranolol's action.

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