Decreased Calcium-Sensing Receptor Expression Controls Calcium Signaling and Cell-To-Cell Adhesion Defects in Aged Skin.
J Invest Dermatol
; 141(11): 2577-2586, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-33862069
ABSTRACT
The calcium-sensing receptor (CaSR) drives essential calcium ion (Ca2+) and E-cadherinâmediated processes in the epidermis, including differentiation, cell-to-cell adhesion, and epidermal barrier homeostasis in cells and in young adult mice. We now report that decreased CaSR expression leads to impaired Ca2+ signal propagation in aged mouse (aged >22 months) epidermis and human (aged >79 years, donor age) keratinocytes. Baseline cytosolic Ca2+ concentrations were higher, and capacitive Ca2+ entry was lower in aged than in young keratinocytes. As in Casr-knockout mice (EpidCaSR-/-), decreased CaSR expression led to decreased E-cadherin and phospholipase C-γ expression and to a compensatory upregulation of STIM1. Pretreatment with the CaSR agonist N-(3-[2-chlorophenyl]propyl)-(R)-alpha-methyl-3-methoxybenzylamine normalized Ca2+ propagation and E-cadherin organization after experimental wounding. These results suggest that age-related defects in CaSR expression dysregulate normal keratinocyte and epidermal Ca2+ signaling, leading to impaired E-cadherin expression, organization, and function. These findings show an innovative mechanism whereby Ca2+- and E-cadherinâdependent functions are impaired in aging epidermis and suggest a new therapeutic approach by restoring CaSR function.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adesão Celular
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Envelhecimento da Pele
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Sinalização do Cálcio
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Receptores de Detecção de Cálcio
Limite:
Aged80
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Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article