Role and mechanism of platelet-derived growth factor BB in thrombocytosis in Kawasaki disease

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics - 25(2023), 6 vom: 15. Juni, Seite 579-586

Sprache:

Chinesisch

Weiterer Titel:

血小板衍生生长因子BB在川崎病血小板增多中的作用及机制研究

Beteiligte Personen:

Shen, Xi-Wei [VerfasserIn]
Tang, Zhi-Yuan [VerfasserIn]
Shen, Xian-Juan [VerfasserIn]
Zhao, Jian-Mei [VerfasserIn]

Links:

Volltext

Themen:

1B56C968OA
8A1O1M485B
Becaplermin
Child
Dami cell
EC 2.7.1.-
EC 2.7.11.1
English Abstract
Imatinib Mesylate
Journal Article
Kawasaki disease
Mouse
Phosphatidylinositol 3-Kinases
Platelet-derived growth factor BB
Proto-Oncogene Proteins c-akt
RNA, Messenger
Thrombocytosis

Anmerkungen:

Date Completed 30.06.2023

Date Revised 07.07.2023

published: Print

Citation Status MEDLINE

doi:

10.7499/j.issn.1008-8830.2301086

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM358834147