Role and mechanism of platelet-derived growth factor BB in thrombocytosis in Kawasaki disease.
10.7499/j.issn.1008-8830.2301086
- Author:
Xi-Wei SHEN
1
;
Zhi-Yuan TANG
;
Xian-Juan SHEN
;
Jian-Mei ZHAO
1
Author Information
1. Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.
- Publication Type:Journal Article
- Keywords:
Child;
Dami cell;
Kawasaki disease;
Mouse;
Platelet-derived growth factor BB;
Thrombocytosis
- MeSH:
Child;
Humans;
Animals;
Mice;
Mice, Inbred C57BL;
Becaplermin;
Imatinib Mesylate/therapeutic use*;
Mucocutaneous Lymph Node Syndrome/drug therapy*;
Phosphatidylinositol 3-Kinases;
Proto-Oncogene Proteins c-akt;
Thrombocytosis/etiology*;
RNA, Messenger
- From:
Chinese Journal of Contemporary Pediatrics
2023;25(6):579-586
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments.
METHODS:ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells.
RESULTS:PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 μmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05).
CONCLUSIONS:PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-β and activating the PI3K/Akt pathway, and the PDGFR-β inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.
