PTEN participates in airway remodeling of asthma by regulating CD38/Ca2+/CREB signaling.
Aging (Albany NY)
; 12(16): 16326-16340, 2020 08 27.
Article
em En
| MEDLINE
| ID: mdl-32889801
ABSTRACT
Both phosphatase and tensin homologue deleted on chromosome ten (PTEN) and cluster of differentiation 38 (CD38) have been suggested to be key regulators of the pathogenesis of asthma. However, the precise role and molecular mechanisms by which PTEN and CD38 are involved in airway remodeling throughout asthma pathogenesis remains poorly understood. This study aimed to elucidate the role of PTEN and CD38 in airway remodeling of asthma. Exposure to tumor necrosis factor-α (TNF-α) in airway smooth muscle (ASM) cells markedly decreased PTEN expression, and increased expression of CD38. Overexpression of PTEN suppressed the expression of CD38 and downregulated proliferation and migration induced by TNF-α stimulation, which was partially reversed by CD38 overexpression. PTEN/CD38 axis regulated Ca2+ levels and cyclic AMP response-element binding protein (CREB) phosphorylation in TNF-α-stimulated ASM cells. The in vitro knockdown of CD38 or overexpression of PTEN remarkably restricted airway remodeling and decreased Ca2+ concentrations and CREB phosphorylation in asthmatic mice. CD38 overexpression abolished the inhibitory effects of PTEN overexpression on airway remodeling. These findings demonstrate that PTEN inhibits airway remodeling of asthma through the downregulation of CD38-mediated Ca2+/CREB signaling, highlighting a key role of PTEN/CD38/Ca2+/CREB signaling in the molecular pathogenesis of asthma.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Traqueia
/
Glicoproteínas de Membrana
/
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
/
Sinalização do Cálcio
/
Miócitos de Músculo Liso
/
PTEN Fosfo-Hidrolase
/
ADP-Ribosil Ciclase 1
/
Remodelação das Vias Aéreas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article