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] |
---|
Links: |
---|
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 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM358834147 | ||
003 | DE-627 | ||
005 | 20231226075604.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||chi c | ||
024 | 7 | |a 10.7499/j.issn.1008-8830.2301086 |2 doi | |
028 | 5 | 2 | |a pubmed24n1196.xml |
035 | |a (DE-627)NLM358834147 | ||
035 | |a (NLM)37382126 | ||
035 | |a (PII)1008-8830(2023)06-0579-08 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a chi | ||
100 | 1 | |a Shen, Xi-Wei |e verfasserin |4 aut | |
245 | 1 | 0 | |a Role and mechanism of platelet-derived growth factor BB in thrombocytosis in Kawasaki disease |
246 | 3 | 3 | |a 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 |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 30.06.2023 | ||
500 | |a Date Revised 07.07.2023 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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) | ||
520 | |a 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 | ||
650 | 4 | |a English Abstract | |
650 | 4 | |a Journal Article | |
650 | 4 | |a Child | |
650 | 4 | |a Dami cell | |
650 | 4 | |a Kawasaki disease | |
650 | 4 | |a Mouse | |
650 | 4 | |a Platelet-derived growth factor BB | |
650 | 4 | |a Thrombocytosis | |
650 | 7 | |a Becaplermin |2 NLM | |
650 | 7 | |a 1B56C968OA |2 NLM | |
650 | 7 | |a Imatinib Mesylate |2 NLM | |
650 | 7 | |a 8A1O1M485B |2 NLM | |
650 | 7 | |a Phosphatidylinositol 3-Kinases |2 NLM | |
650 | 7 | |a EC 2.7.1.- |2 NLM | |
650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
650 | 7 | |a EC 2.7.11.1 |2 NLM | |
650 | 7 | |a RNA, Messenger |2 NLM | |
700 | 1 | |a Tang, Zhi-Yuan |e verfasserin |4 aut | |
700 | 1 | |a Shen, Xian-Juan |e verfasserin |4 aut | |
700 | 1 | |a Zhao, Jian-Mei |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics |d 2006 |g 25(2023), 6 vom: 15. Juni, Seite 579-586 |w (DE-627)NLM161132898 |x 1008-8830 |7 nnns |
773 | 1 | 8 | |g volume:25 |g year:2023 |g number:6 |g day:15 |g month:06 |g pages:579-586 |
856 | 4 | 0 | |u http://dx.doi.org/10.7499/j.issn.1008-8830.2301086 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 25 |j 2023 |e 6 |b 15 |c 06 |h 579-586 |