CFTR Regulates Platelet Activation via the P2Y12-Mediated Signaling Pathway
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0406
- VernacularTitle:CFTR通过调控二磷酸腺苷受体P2Y12影响血小板活化
- Author:
Jun LI
1
;
Han-yan YANG
1
;
Hui HAN
1
;
Mei LI
2
;
Guan-lei WANG
1
Author Information
1. Department of Pharmacology， Cardiac and Cerebral Vascular Research Center， Zhongshan School of Medicine， Sun Yat-sen University， Guangzhou 510080， China
2. VIP Healthcare Center， The Third Affiliated Hospital of Sun Yat-sen University， Guangzhou 510630， China
- Publication Type:Journal Article
- Keywords:
CFTR;
P2Y12;
platelet;
activation
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(4):521-527
- CountryChina
- Language:Chinese
-
Abstract:
ObjectivePlatelet activation mediated by adenosine diphosphate receptor P2Y12 is critical for platelet activation and thrombosis formation. The goal of the presented study was to investigate the role of CFTR in platelet activation mediated by P2Y12. Methods8-week-old CFTR knockout （Cftr-/-） mice and age-matched wild-type （Cftr+/+） mice were used to set up collagen and epinephrine-induced pulmonary embolism mouse models. The lung sections were prepared to observe the pulmonary embolism. The circulating platelets were isolated from peripheral blood of Cftr-/- and Cftr+/+ mice， and were used to detect protein expressions of P2Y12， p-PI3K and p-AKT by western blot analysis. The above signaling proteins were also detected in human-derived megakaryocyte cell strains （Meg-01） treated with different concentration of adenosine diphosphate （ADP）. CFTRinh-172， a selective CFTR chloride channel blocker was also applied to observe how CFTR affected the protein level of P2Y12 in Meg-01 cells. ResultsIn the pulmonary embolism model， the embolization area in lung tissue sections from Cftr-/- mice were significantly larger than that of Cftr+/+ mice. Compared with Cftr+/+ mice， the protein expression of P2Y12， p-PI3K and p-AKT in circulating platelets of Cftr-/- mice was significantly elevated. However， no change was found in the protein expression of platelet CFTR in P2Y12 knockout mice， which suggested that CFTR might be in the upstream of P2Y12 in the regulating mechanism of platelet activation. In Meg-01 cells， ADP concentration-dependently induced P2Y12 protein expression but decreased CFTR expression. The incubation of Meg-01 cells with CFTRInh-172 could significantly increase P2Y12 expression. ConclusionsThis study revealed a new mechanism of platelet activation， that is， CFTR may regulate platelet activation by regulating P2Y12-mediated signaling pathway.
