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- PMID: 20643953
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Article: Leptin signaling maintains B-cell homeostasis via induction of Bcl-2 and cyclin D1
Title | Leptin signaling maintains B-cell homeostasis via induction of Bcl-2 and cyclin D1 | ||||
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Authors | |||||
Keywords | Apoptosis B cell survival microRNA Proliferation | ||||
Issue Date | 2010 | ||||
Publisher | National 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? | ||||
Abstract | Regulation 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 Identifier | http://hdl.handle.net/10722/129510 | ||||
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 | ||||
PubMed Central ID | |||||
ISI Accession Number ID |
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 Field | Value | Language |
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dc.contributor.author | Lam, QLK | en_HK |
dc.contributor.author | Wang, S | en_HK |
dc.contributor.author | Ko, OKH | en_HK |
dc.contributor.author | Kincade, PW | en_HK |
dc.contributor.author | Lu, L | en_HK |
dc.date.accessioned | 2010-12-23T08:38:17Z | - |
dc.date.available | 2010-12-23T08:38:17Z | - |
dc.date.issued | 2010 | en_HK |
dc.identifier.citation | Proceedings Of The National Academy Of Sciences Of The United States Of America, 2010, v. 107 n. 31, p. 13812-13817 | en_HK |
dc.identifier.issn | 0027-8424 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/129510 | - |
dc.description.abstract | Regulation 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.language | eng | en_US |
dc.publisher | National Academy of Sciences. The Journal's web site is located at http://www.pnas.org | en_HK |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | en_HK |
dc.subject | Apoptosis | en_HK |
dc.subject | B cell survival | en_HK |
dc.subject | microRNA | en_HK |
dc.subject | Proliferation | en_HK |
dc.subject.mesh | B-Lymphocytes - cytology - immunology - metabolism | - |
dc.subject.mesh | Cyclin D1 - genetics - immunology | - |
dc.subject.mesh | Homeostasis | - |
dc.subject.mesh | Leptin - immunology - metabolism | - |
dc.subject.mesh | Proto-Oncogene Proteins c-bcl-2 - genetics - immunology | - |
dc.title | Leptin signaling maintains B-cell homeostasis via induction of Bcl-2 and cyclin D1 | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://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+D1 | en_US |
dc.identifier.email | Lam, QLK: qlam@pathology.hku.hk | en_HK |
dc.identifier.email | Lu, L: liweilu@hkucc.hku.hk | en_HK |
dc.identifier.authority | Lam, QLK=rp00312 | en_HK |
dc.identifier.authority | Lu, L=rp00477 | en_HK |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1073/pnas.1004185107 | en_HK |
dc.identifier.pmid | 20643953 | - |
dc.identifier.pmcid | PMC2922219 | - |
dc.identifier.scopus | eid_2-s2.0-77956373481 | en_HK |
dc.identifier.hkuros | 176948 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-77956373481&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 107 | en_HK |
dc.identifier.issue | 31 | en_HK |
dc.identifier.spage | 13812 | en_HK |
dc.identifier.epage | 13817 | en_HK |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:000280605900048 | - |
dc.publisher.place | United States | en_HK |
dc.relation.project | Role of leptin in regulating B cell maturation and function | - |
dc.identifier.scopusauthorid | Lam, QLK=8722491000 | en_HK |
dc.identifier.scopusauthorid | Wang, S=23500575700 | en_HK |
dc.identifier.scopusauthorid | Ko, OKH=8119962000 | en_HK |
dc.identifier.scopusauthorid | Kincade, PW=7101815790 | en_HK |
dc.identifier.scopusauthorid | Lu, L=7403963552 | en_HK |
dc.identifier.issnl | 0027-8424 | - |