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Article: Platelet-derived growth factor enhances platelet recovery in a murine model of radiation-induced thrombocytopenia and reduces apoptosis in megakaryocytes via its receptors and the PI3-k/Akt pathway

TitlePlatelet-derived growth factor enhances platelet recovery in a murine model of radiation-induced thrombocytopenia and reduces apoptosis in megakaryocytes via its receptors and the PI3-k/Akt pathway
Authors
KeywordsApoptosis
Imatinib mesylate
Platelet-derived growth factor
Thrombocytopenia
Thrombopoiesis
Issue Date2010
PublisherFondazione Ferrata Storti.
Citation
Haematologica, 2010, v. 95 n. 10, p. 1745-1753 How to Cite?
AbstractBackground Platelet-derived growth factor is involved in the regulation of hematopoiesis. Imatinib mesylate, a platelet-derived growth factor receptor inhibitor, induces thrombocytopenia in a significant proportion of patients with chronic myeloid leukemia. Although our previous studies showed that platelet-derived growth factor enhances megakaryocytopoiesis in vitro, the in vivo effect of platelet-derived growth factor in a model of radiation-induced thrombocytopenia has not been reported. Design and Methods In this study, we investigated the effect of platelet-derived growth factor on hematopoietic stem/progenitor cells and platelet production using an irradiated-mouse model. We also explored the potential molecular mechanisms of platelet-derived growth factor on thrombopoiesis in M-07e cells. Results Platelet-derived growth factor, like thrombopoietin, significantly promoted the recovery of platelets and the formation of bone marrow colony-forming unit-megakaryocyte in irradiated mice. Histology confirmed the protective effect of platelet-derived growth factor, as shown by an increased number of hematopoietic stem/progenitor cells and a reduction of apoptosis. In a megakaryocytic apoptotic model, platelet-derived growth factor had a similar anti-apoptotic effect as thrombopoietin on megakaryocytes. We also demonstrated that platelet-derived growth factor activated the PI3-k/Akt signaling pathway, while addition of imatinib mesylate reduced p-Akt expression. Conclusions Our findings show that platelet-derived growth factor enhances platelet recovery in mice with radiation-induced thrombocytopenia. This radioprotective effect is likely to be mediated via platelet-derived growth factor receptors with subsequent activation of the PI3-k/Akt pathway. We also provide a possible explanation that blockage of platelet-derived growth factor receptors may reduce thrombopoiesis and play a role in imatinib mesylate-induced thrombocytopenia. © 2010 Ferrata Storti Foundation.
Persistent Identifierhttp://hdl.handle.net/10722/125239
ISSN
2015 Impact Factor: 6.671
2015 SCImago Journal Rankings: 3.010
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
Funding Information:

this work was supported in part by Seed Funding for Basic Research, The University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorYe, JYen_HK
dc.contributor.authorChan, GCFen_HK
dc.contributor.authorQiao, Len_HK
dc.contributor.authorLian, Qen_HK
dc.contributor.authorMeng, FYen_HK
dc.contributor.authorLuo, XQen_HK
dc.contributor.authorKhachigian, LMen_HK
dc.contributor.authorMa, Men_HK
dc.contributor.authorDeng, Ren_HK
dc.contributor.authorChen, JLen_HK
dc.contributor.authorChong, BHen_HK
dc.contributor.authorYang, Men_HK
dc.date.accessioned2010-10-31T11:19:21Z-
dc.date.available2010-10-31T11:19:21Z-
dc.date.issued2010en_HK
dc.identifier.citationHaematologica, 2010, v. 95 n. 10, p. 1745-1753en_HK
dc.identifier.issn0390-6078en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125239-
dc.description.abstractBackground Platelet-derived growth factor is involved in the regulation of hematopoiesis. Imatinib mesylate, a platelet-derived growth factor receptor inhibitor, induces thrombocytopenia in a significant proportion of patients with chronic myeloid leukemia. Although our previous studies showed that platelet-derived growth factor enhances megakaryocytopoiesis in vitro, the in vivo effect of platelet-derived growth factor in a model of radiation-induced thrombocytopenia has not been reported. Design and Methods In this study, we investigated the effect of platelet-derived growth factor on hematopoietic stem/progenitor cells and platelet production using an irradiated-mouse model. We also explored the potential molecular mechanisms of platelet-derived growth factor on thrombopoiesis in M-07e cells. Results Platelet-derived growth factor, like thrombopoietin, significantly promoted the recovery of platelets and the formation of bone marrow colony-forming unit-megakaryocyte in irradiated mice. Histology confirmed the protective effect of platelet-derived growth factor, as shown by an increased number of hematopoietic stem/progenitor cells and a reduction of apoptosis. In a megakaryocytic apoptotic model, platelet-derived growth factor had a similar anti-apoptotic effect as thrombopoietin on megakaryocytes. We also demonstrated that platelet-derived growth factor activated the PI3-k/Akt signaling pathway, while addition of imatinib mesylate reduced p-Akt expression. Conclusions Our findings show that platelet-derived growth factor enhances platelet recovery in mice with radiation-induced thrombocytopenia. This radioprotective effect is likely to be mediated via platelet-derived growth factor receptors with subsequent activation of the PI3-k/Akt pathway. We also provide a possible explanation that blockage of platelet-derived growth factor receptors may reduce thrombopoiesis and play a role in imatinib mesylate-induced thrombocytopenia. © 2010 Ferrata Storti Foundation.en_HK
dc.languageengen_HK
dc.publisherFondazione Ferrata Storti.-
dc.relation.ispartofHaematologicaen_HK
dc.subjectApoptosisen_HK
dc.subjectImatinib mesylateen_HK
dc.subjectPlatelet-derived growth factoren_HK
dc.subjectThrombocytopeniaen_HK
dc.subjectThrombopoiesisen_HK
dc.subject.meshApoptosis - drug effects-
dc.subject.meshBlood Platelets - drug effects - radiation effects-
dc.subject.meshMegakaryocytes - pathology-
dc.subject.meshPlatelet-Derived Growth Factor - pharmacology - therapeutic use-
dc.subject.meshThrombocytopenia - drug therapy - etiology-
dc.titlePlatelet-derived growth factor enhances platelet recovery in a murine model of radiation-induced thrombocytopenia and reduces apoptosis in megakaryocytes via its receptors and the PI3-k/Akt pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0390-6078&volume=95&issue=10&spage=1745&epage=1753&date=2010&atitle=Platelet-derived+growth+factor+enhances+platelet+recovery+in+a+murine+model+of+radiation-induced+thrombocytopenia+and+reduces+apoptosis+in+megakaryocytes+via+its+receptors+and+the+PI3-k/Akt+pathway-
dc.identifier.emailChan, GCF: gcfchan@hku.hken_HK
dc.identifier.emailQiao, L: lq8688@hotmail.comen_HK
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hken_HK
dc.identifier.authorityChan, GCF=rp00431en_HK
dc.identifier.authorityQiao, L=rp00513en_HK
dc.identifier.authorityLian, Q=rp00267en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.3324/haematol.2009.020958en_HK
dc.identifier.pmid20562316-
dc.identifier.pmcidPMC2948101-
dc.identifier.scopuseid_2-s2.0-77957771466en_HK
dc.identifier.hkuros179094en_HK
dc.identifier.hkuros204427-
dc.identifier.hkuros206956-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77957771466&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume95en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1745en_HK
dc.identifier.epage1753en_HK
dc.identifier.eissn1592-8721-
dc.identifier.isiWOS:000283275000019-
dc.publisher.placeItalyen_HK
dc.identifier.scopusauthoridYe, JY=23669624100en_HK
dc.identifier.scopusauthoridChan, GCF=16160154400en_HK
dc.identifier.scopusauthoridQiao, L=7202151719en_HK
dc.identifier.scopusauthoridLian, Q=7003399023en_HK
dc.identifier.scopusauthoridMeng, FY=26967935100en_HK
dc.identifier.scopusauthoridLuo, XQ=7402871254en_HK
dc.identifier.scopusauthoridKhachigian, LM=26643419000en_HK
dc.identifier.scopusauthoridMa, M=37073032200en_HK
dc.identifier.scopusauthoridDeng, R=35209695100en_HK
dc.identifier.scopusauthoridChen, JL=36626925300en_HK
dc.identifier.scopusauthoridChong, BH=7101803569en_HK
dc.identifier.scopusauthoridYang, M=7404927250en_HK

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