[1]吕枭锐 龚凤英.Hepassocin:一种新型的肝细胞因子[J].国际内分泌代谢杂志,2019,39(05):332-336.[doi:10.3760/cma.j.issn.1673-4157.2019.05.011]
 Lyu Xiaorui,Gong Fengying.Hepassocin: a novel hepatokine[J].International Journal of Endocrinology and Metabolism,2019,39(05):332-336.[doi:10.3760/cma.j.issn.1673-4157.2019.05.011]
点击复制

Hepassocin:一种新型的肝细胞因子()
分享到:

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
39
期数:
2019年05期
页码:
332-336
栏目:
综述
出版日期:
2019-09-20

文章信息/Info

Title:
Hepassocin: a novel hepatokine
作者:
吕枭锐 龚凤英
中国医学科学院,中国协和医科大学,北京协和医院内分泌科,卫生健康委内分泌重点实验室,协和转化医学中心,北京 100730
Author(s):
Lyu Xiaorui Gong Fengying
Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, The Translational Medicine Center of PUMCH, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
关键词:
Hepassocin 肝细胞增殖 非酒精性脂肪性肝病 胰岛素抵抗 2型糖尿病
Keywords:
Hepassocin Hepatocyte proliferation Nonalcoholic fatty liver disease Insulin resistance Type 2 diabetes mellitus
DOI:
10.3760/cma.j.issn.1673-4157.2019.05.011
摘要:
Hepassocin(HPS)是一种肝细胞特异性分泌的蛋白质。研究发现,HPS能促进正常肝细胞增殖,抑制肝癌细胞增殖。HPS在急性肝损伤时能通过抑制肝细胞凋亡保护肝脏,并具有减轻高血糖所导致的肝细胞氧化应激的作用。在非酒精性脂肪性肝病(NAFLD)患者中,HPS的表达和分泌增多,其能诱导肝脂质合成和聚集。而在2型糖尿病患者中,血浆HPS浓度显著增加, 与肝脏和骨骼肌等组织、器官的胰岛素抵抗有关。这些研究表明,HPS不仅可以调控肝细胞增殖和凋亡,还能参与NAFLD和2型糖尿病的发生、发展。
Abstract:
Hepassocin(HPS)is a hepatocyte-specific secreted protein. Studies found that HPS could promote the proliferation of normal hepatocytes, whereas inhibited the proliferation of liver cancer cells. It can protect the liver through inhibition of hepatocytes apoptosis in the case of acute liver injury, and improve oxidative stress induced by hyperglycemia in hepatocytes. The expression and secretion of HPS are significantly increased in patients with nonalcoholic fatty liver disease(NAFLD), and it can induce production and aggregation of liver fat. In addition, the plasma concentration of HPS is significantly increased in patients with type 2 diabetes, and it induces insulin resistance of liver and skeletal muscle tissues. These studies indicate that HPS is not only involved in the proliferation and apoptosis of hepatocytes, but also the development of NAFLD and diabetes.

参考文献/References:

[1] Younossi ZM,Koenig AB,Abdelatif D,et al. Global epidemiology of nonalcoholic fatty liver disease--meta-analytic assessment of prevalence, incidence, and outcomes[J].Hepatology,2016,64(1):73-84.DOI:10.1002/hep.28431.
[2] Bellentani S,Saccoccio G,Masutti F,et al.Prevalence of and risk factors for hepatic steatosis in Northern Italy[J].Ann Intern Med,2000,132(2):112-117. DOI:10.7326/0003-4819-132-2-200001180-00004.
[3] Luyckx FH,Desaive C,Thiry A,et al.Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty[J].Int J Obes Relat Metab Disord,1998,22(3):222-226.
[4] GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015[J].Lancet,2016,388(10053):1545-1602.DOI:10.1016/S0140-6736(16)31678-6.
[5] Tfayli H,Arslanian S.Pathophysiology of type 2 diabetes mellitus in youth: the evolving chameleon[J].Arq Bras Endocrinol Metabol,2009,53(2):165-174.
[6] Imperatore G,Boyle JP,Thompson TJ,et al.Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2050: dynamic modeling of incidence, mortality, and population growth[J].Diabetes Care,2012,35(12):2515-2520.DOI:10.2337/dc12-0669.
[7] Hara H,Uchida S,Yoshimura H,et al.Isolation and characterization of a novel liver-specific gene, hepassocin, upregulated during liver regeneration[J].Biochim Biophys Acta,2000,1492(1):31-44.DOI:10.1016/s0167-4781(00)00056-7.
[8] Hara H,Yoshimura H,Uchida S,et al.Molecular cloning and functional expression analysis of a cDNA for human hepassocin, a liver-specific protein with hepatocyte mitogenic activity[J].Biochim Biophys Acta,2001,1520(1):45-53.DOI:10.1016/s0167-4781(01)00249-4.
[9] Yan J,Yu Y,Wang N,et al.LFIRE-1/HFREP-1,a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma[J].Oncogene,2004,23(10):1939-1949.DOI:10.1038/sj.onc.1207306.
[10] Ou HY,Wu HT,Lin CH,et al.The hepatic protection effects of hepassocin in hyperglycemic crisis[J].J Clin Endocrinol Metab,2017,102(7):2407-2415.DOI:10.1210/jc.2016-3287.
[11] Yu HT,Yu M,Li CY,et al.Specific expression and regulation of hepassocin in the liver and down-regulation of the correlation of HNF1alpha with decreased levels of hepassocin in human hepatocellular carcinoma[J].J Biol Chem,2009,284(20):13335-13347.DOI:10.1074/jbc.M806393200.
[12] Cheng KP,Ou HY,Hung HC,et al.Unsaturated fatty acids increase the expression of hepassocin through a signal transducer and activator of transcription 3-dependent pathway in HepG2 cells[J].Lipids,2018,53(9):863-869.DOI:10.1002/lipd.12099.
[13] Jung TW,Chung YH,Kim HC,et al.Hyperlipidemia-induced hepassocin in the liver contributes to insulin resistance in skeletalmuscle[J].Mol Cell Endocrinol,2018,470:26-33.DOI:10.1016/j.mce.2017.10.014.
[14] Wu HT,Lu FH,Ou HY,et al.The role of hepassocin in the development of non-alcoholic fatty liver disease[J].J Hepatol,2013,59(5):1065-1072.DOI:10.1016/j.jhep.2013.06.004.
[15] Gao M,Yan H,Yin RH,et al.Hepassocin is required for hepatic outgrowth during zebrafish hepatogenesis[J].Biochem Biophys Res Commun,2015,463(3):466-471.DOI:10.1016/j.bbrc.2015.05.121.
[16] Cao MM,Xu WX,Li CY,et al.Hepassocin regulates cell proliferation of the human hepatic cells L02 and hepatocarcinoma cells through different mechanisms[J].J Cell Biochem,2011,112(10):2882-2890.DOI:10.1002/jcb.23202.
[17] Li CY,Cao CZ,Xu WX,et al.Recombinant human hepassocin stimulates proliferation of hepatocytes in vivo and improves survival in rats with fulminant hepatic failure[J].Gut,2010,59(6):817-826.DOI:10.1136/gut.2008.171124.
[18] Gao M,Zhan YQ,Yu M,et al.Hepassocin activates the EGFR/ERK cascade and induces proliferation of L02 cells through the Src-dependent pathway[J].Cell Signal,2014,26(10):2161-2166.DOI:10.1016/j.cellsig.2014.04.013.
[19] Demchev V,Malana G,Vangala D,et al.Targeted deletion of fibrinogen like protein 1 reveals a novel role in energy substrate utilization[J].PLoS One,2013,8(3):e58084.DOI:10.1371/journal.pone.0058084.
[20] Nayeb-Hashemi H,Desai A,Demchev V,et al.Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development[J].Biochem Biophys Res Commun,2015,465(2):167-173.DOI:10.1016/j.bbrc.2015.07.078.
[21] Zou Z,Cai Y,Chen Y,et al.Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3[J].Mol Med Rep,2015,12(2):2089-2097.DOI:10.3892/mmr.2015.3660.
[22] Rijken DC,Dirkx SP,Luider TM,et al.Hepatocyte-derived fibrinogen-related protein-1 is associated with the fibrin matrix of a plasmaclot[J].Biochem Biophys Res Commun,2006,350(1):191-194.DOI:10.1016/j.bbrc.2006.09.018.
[23] Liu Z, Ukomadu C.Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant[J].Biochem Biophys Res Commun,2008,365(4):729-734.DOI:10.1016/j.bbrc.2007.11.069.
[24] Fu S,Fan J,Blanco J,et al.Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting[J].PLoS Genet,2012,8(8):e1002902.DOI:10.1371/journal.pgen.1002902.
[25] Abdelmoemen G,Khodeir SA,Zaki AN,et al.Overexpression of hepassocin in diabetic patients with nonalcoholic fatty liver disease may facilitate increased hepatic lipid accumulation[J].Endocr Metab Immune Disord Drug Targets,2019,19(2):185-188.DOI:10.2174/1871530318666180716100543.
[26] Sreekumar R,Rosado B,Rasmussen D,et al.Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis[J].Hepatology,2003,38(1):244-251.DOI:10.1053/jhep.2003.50290.
[27] Wu HT,Ou HY,Hung HC,et al.A novel hepatokine, HFREP1, plays a crucial role in the development of insulin resistance and type 2 diabetes[J].Diabetologia,2016,59(8):1732-1742.DOI:10.1007/s00125-016-3991-7.

备注/Memo

备注/Memo:
通信作者:龚凤英,Email:fygong@sina.com,fygong@aliyun.com
Corresponding author: Gong Fengying, Email:fygong@sina.com, fygong@aliyun.com
基金项目:北京市自然科学基金(7182130,7082079); 国家自然科学基金(81370898,30771026,30540036); 人社部留学人员科技活动项目择优资助经费(启动类); 国家临床重点专科建设项目单位(WBYZ2011-873)
Fund program:Natural Science Foundation of Beijing of China(7182130, 7082079); National Natural Science Foundation of China(81370898, 30771026, 30540036); Scientific Research Foundation for the Selected Returned Overseas Chinese Scholars, Ministry of Human Resources and Social Security of China(Start-up); National Key Program of Clinical Science(WBYZ2011-873)
更新日期/Last Update: 2019-09-20