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学科主题: 基础医学
题名:
Liver Is the Major Source of Elevated Serum Lipocalin-2 Levels After Bacterial Infection or Partial Hepatectomy: A Critical Role for IL-6/STAT3
作者: Xu, Ming-Jiang1,2; Feng, Dechun1; Wu, Hailong3; Wang, Hua1; Chan, Yvonne4; Kolls, Jay5; Borregaard, Niels6; Porse, Bo7,8,9; Berger, Thorsten10; Mak, Tak W.10; Cowland, Jack B.6; Kong, Xiaoni1,3,11,12; Gao, Bin1
刊名: HEPATOLOGY
发表日期: 2015-02-01
DOI: 10.1002/hep.27447
卷: 61, 期:2, 页:692-702
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology
研究领域[WOS]: Gastroenterology & Hepatology
关键词[WOS]: GELATINASE-ASSOCIATED LIPOCALIN ; NEUTROPHIL GELATINASE ; SIGNAL TRANSDUCER ; TRANSCRIPTION 3 ; HOST-DEFENSE ; MICE ; INJURY ; REGENERATION ; INFLAMMATION ; NGAL
英文摘要:

Lipocalin-2 (LCN2) was originally isolated from human neutrophils and termed neutrophil gelatinase-associated lipocalin (NGAL). However, the functions of LCN2 and the cell types that are primarily responsible for LCN2 production remain unclear. To address these issues, hepatocyte-specific Lcn2 knockout (Lcn2(Hep-/-)) mice were generated and subjected to bacterial infection (with Klesbsiella pneumoniae or Escherichia coli) or partial hepatectomy (PHx). Studies of Lcn2(Hep-/-) mice revealed that hepatocytes contributed to 25% of the low basal serum level of LCN2 protein (approximate to 62 ng/mL) but were responsible for more than 90% of the highly elevated serum LCN2 protein level (approximate to 6,000 ng/mL) postinfection and more than 60% post-PHx (approximate to 700 ng/mL). Interestingly, both Lcn2(Hep-/-) and global Lcn2 knockout (Lcn2(-/-)) mice demonstrated comparable increases in susceptibility to infection with K. pneumoniae or E. coli. These mice also had increased enteric bacterial translocation from the gut to the mesenteric lymph nodes and exhibited reduced liver regeneration after PHx. Treatment with interleukin (IL)-6 stimulated hepatocytes to produce LCN2 in vitro and in vivo. Hepatocyte-specific ablation of the IL-6 receptor or Stat3, a major downstream effector of IL-6, markedly abrogated LCN2 elevation in vivo. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed that STAT3 was recruited to the promoter region of the Lcn2 gene upon STAT3 activation by IL-6. Conclusion: Hepatocytes are the major cell type responsible for LCN2 production after bacterial infection or PHx, and this response is dependent on IL-6 activation of the STAT3 signaling pathway. Thus, hepatocyte-derived LCN2 plays an important role in inhibiting bacterial infection and promoting liver regeneration. (Hepatology 2015;61:692-702)

语种: 英语
所属项目编号: 90-13-02
项目资助者: NIAAA, NIH ; NIAAA, NIH (State Key Laboratory of Oncogenes and Related Genes)
WOS记录号: WOS:000348563200032
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62774
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA
2.Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol,Hlth Sci Ctr, Minist Educ,Key Lab Mol Cardiovasc Sci, Beijing 100871, Peoples R China
3.Shanghai Jiao Tong Univ, Renji Med Clin Stem Cell Res Ctr 10, State Key Lab Oncogenes & Related Genes, Ren Ji Hosp,Sch Med, Shanghai 200030, Peoples R China
4.Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA
5.Childrens Hosp Pittsburgh, Richard King Mellon Fdn, Pediat Res Inst, Pittsburgh, PA 15213 USA
6.Rigshosp, Granulocyte Res Lab, DK-2100 Copenhagen, Denmark
7.Univ Copenhagen, Finsen Lab, Rigshosp, Fac Hlth Sci, DK-1168 Copenhagen, Denmark
8.Univ Copenhagen, BRIC, DK-1168 Copenhagen, Denmark
9.Univ Copenhagen, Danish Stem Cell Ctr DanStem, Fac Hlth Sci, DK-1168 Copenhagen, Denmark
10.Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON, Canada
11.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China
12.Shanghai Jiao Tong Univ, Med Res Inst 10, Shanghai 200030, Peoples R China

Recommended Citation:
Xu, Ming-Jiang,Feng, Dechun,Wu, Hailong,et al. Liver Is the Major Source of Elevated Serum Lipocalin-2 Levels After Bacterial Infection or Partial Hepatectomy: A Critical Role for IL-6/STAT3[J]. HEPATOLOGY,2015,61(2):692-702.
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