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Article: Leptin signaling maintains B-cell homeostasis via induction of Bcl-2 and cyclin D1

TitleLeptin signaling maintains B-cell homeostasis via induction of Bcl-2 and cyclin D1
Authors
KeywordsApoptosis
B cell survival
microRNA
Proliferation
Issue Date2010
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2010, v. 107 n. 31, p. 13812-13817 How to Cite?
AbstractRegulation of apoptosis and cell cycle progression plays an essential role in the maintenance of B-cell homeostasis, because a fine balance of survival and expansion is critical for preventing lymphocytic disorders. Although remarkable progress in understanding B-cell development has been achieved, much less is known concerning niches that are critical to the maintenance of B-cell homeostasis. Leptin has recently been recognized to be important for modulating the immune responses, but it has remained unclear how leptin signaling influences B-cell physiology. A variety of lymphocytic malignancies have been reported to be linked to leptin, and therefore it is necessary to elucidate the mechanisms involved. Here we demonstrate that leptin promotes B-cell homeostasis by inhibiting apoptosis and by inducing cell cycle entry through the activation of expressions of B-cell CLL/lymphoma 2 (Bcl-2) and cyclin D1. We further show that leptin can induce Bcl-2 and cyclin D1 expression by two pathways, including the direct activation of their promoters and suppression of microRNAs (miRNAs) that target their putative 3′ untranslated regions. Amplification of these leptin-modulated miRNAs inhibited B lymphoma cell growth. These findings provide insights into mechanisms for leptin regulation of the humoral immune system and suggest new therapeutic strategies for leptin receptor expressing malignancies.
Persistent Identifierhttp://hdl.handle.net/10722/129510
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 771809M
HKU 200909159002
HKU 20087176006
Funding Information:

We thank Dr. Lin Zheng for excellent technical assistance. This work was supported by Research Grants Council of Hong Kong Grants HKU 771809M (to L. L.) and HKU 200909159002 and HKU 20087176006 (to Q. L. K. L.).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLam, QLKen_HK
dc.contributor.authorWang, Sen_HK
dc.contributor.authorKo, OKHen_HK
dc.contributor.authorKincade, PWen_HK
dc.contributor.authorLu, Len_HK
dc.date.accessioned2010-12-23T08:38:17Z-
dc.date.available2010-12-23T08:38:17Z-
dc.date.issued2010en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2010, v. 107 n. 31, p. 13812-13817en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129510-
dc.description.abstractRegulation of apoptosis and cell cycle progression plays an essential role in the maintenance of B-cell homeostasis, because a fine balance of survival and expansion is critical for preventing lymphocytic disorders. Although remarkable progress in understanding B-cell development has been achieved, much less is known concerning niches that are critical to the maintenance of B-cell homeostasis. Leptin has recently been recognized to be important for modulating the immune responses, but it has remained unclear how leptin signaling influences B-cell physiology. A variety of lymphocytic malignancies have been reported to be linked to leptin, and therefore it is necessary to elucidate the mechanisms involved. Here we demonstrate that leptin promotes B-cell homeostasis by inhibiting apoptosis and by inducing cell cycle entry through the activation of expressions of B-cell CLL/lymphoma 2 (Bcl-2) and cyclin D1. We further show that leptin can induce Bcl-2 and cyclin D1 expression by two pathways, including the direct activation of their promoters and suppression of microRNAs (miRNAs) that target their putative 3′ untranslated regions. Amplification of these leptin-modulated miRNAs inhibited B lymphoma cell growth. These findings provide insights into mechanisms for leptin regulation of the humoral immune system and suggest new therapeutic strategies for leptin receptor expressing malignancies.en_HK
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectApoptosisen_HK
dc.subjectB cell survivalen_HK
dc.subjectmicroRNAen_HK
dc.subjectProliferationen_HK
dc.subject.meshB-Lymphocytes - cytology - immunology - metabolism-
dc.subject.meshCyclin D1 - genetics - immunology-
dc.subject.meshHomeostasis-
dc.subject.meshLeptin - immunology - metabolism-
dc.subject.meshProto-Oncogene Proteins c-bcl-2 - genetics - immunology-
dc.titleLeptin signaling maintains B-cell homeostasis via induction of Bcl-2 and cyclin D1en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=107&issue=31&spage=13812&epage=13817&date=2010&atitle=Leptin+signaling+maintains+B-cell+homeostasis+via+induction+of+Bcl-2+and+Cyclin+D1en_US
dc.identifier.emailLam, QLK: qlam@pathology.hku.hken_HK
dc.identifier.emailLu, L: liweilu@hkucc.hku.hken_HK
dc.identifier.authorityLam, QLK=rp00312en_HK
dc.identifier.authorityLu, L=rp00477en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1004185107en_HK
dc.identifier.pmid20643953-
dc.identifier.pmcidPMC2922219-
dc.identifier.scopuseid_2-s2.0-77956373481en_HK
dc.identifier.hkuros176948en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956373481&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume107en_HK
dc.identifier.issue31en_HK
dc.identifier.spage13812en_HK
dc.identifier.epage13817en_HK
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000280605900048-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectRole of leptin in regulating B cell maturation and function-
dc.identifier.scopusauthoridLam, QLK=8722491000en_HK
dc.identifier.scopusauthoridWang, S=23500575700en_HK
dc.identifier.scopusauthoridKo, OKH=8119962000en_HK
dc.identifier.scopusauthoridKincade, PW=7101815790en_HK
dc.identifier.scopusauthoridLu, L=7403963552en_HK

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