P2Y2 receptor promotes intestinal microtubule stabilization and mucosal re-epithelization in experimental colitis.
J Cell Physiol
; 228(1): 99-109, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-22553130
ABSTRACT
P2Y(2) receptor expression is increased in intestinal epithelial cells (IECs) during inflammatory bowel diseases (IBDs). In this context, P2Y(2) stimulates PGE(2) release by IECs, suggesting a role in wound healing. For this study, we have used the non-cancerous IEC-6 cell line. IEC-6 cell migration was determined using Boyden chambers and the single-edged razor blade model of wounding. The receptor was activated using ATP, UTP, or 2-thioUTP. Pharmacological inhibitors, a blocking peptide, a neutralizing antibody and interfering RNAs were used to characterize the signaling events. Focal adhesions and microtubule (MT) dynamics were determined by immunofluorescence using anti-vinculin and anti-acetylated-α-tubulin antibodies, respectively. In vivo, the dextran sodium sulfate mouse model of colitis was used to characterize the effects of P2Y(2) agonist 2-thioUTP on remission. We showed that P2Y(2) increased cell migration and wound closure by recruiting Go protein with the cooperation of integrin α(v) . Following P2Y(2) activation, we demonstrated that GSK3ß activity was inhibited in response to Akt activation. This leads to MT stabilization and increased number of focal adhesions. In vivo, P2Y(2) activation stimulates remission, as illustrated by a reduction in the disease activity index values and histological scores as compared to control mice. These findings highlight a novel function for this receptor in IECs. They also illustrate that P2Y receptors could be targeted for the development of innovative therapies for the treatment of IBDs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Colite
/
Células Epiteliais
/
Receptores Purinérgicos P2Y2
/
Mucosa Intestinal
/
Microtúbulos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2013
Tipo de documento:
Article