二肽基肽酶-4在慢性肝病发病中的作用研究进展

doi:10.3969/j.issn.1672-5069.2016.05.035

Abstract

Abstract: Dipeptidyl peptidase-4（DPP-4） is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and has pleiotropic effects. A representative target peptide is glucagon-like peptide-1 （GLP-1）,and inactivation of GLP-1 results in the development of glucose intolerance/diabetes mellitus. In addition to its peptidase activity,DPP-4 is associated with immune stimulation, binding to and degradation of extracellular matrix,resistance to anti-cancer agents,and lipid accumulation. The liver expresses DPP-4 to a higher degree,and recent studies suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection,non-alcoholic fatty liver disease,and hepatocellular carcinoma. Furthermore,hepatic stem cells express DPP-4,which might plays a crucial role in hepatic regeneration. In this paper,we reviewed the tissue distribution and various biological effects of DPP-4. The impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor were also discussed.

Key words: Viral hepatitis, Non-alcoholic fatty liver disease, Dipeptidyl peptidase-4, Incretin, Insulin resistance

Zhang Tingting, Wang Xuan.. What roles does dipeptidyl peptidase-4 play in chronic liver diseases?[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(5): 637-640.

References

[1] Misumi Y,Hayashi Y,Arakawa F,et al. Molecular cloning and sequence analysis of human dipeptidyl peptidase IV a serine proteinase on the cell surface. Biochim Biophys Acta,1992,1131: 333-336.
[2] Kikuchi M,Fukuyama K,Epstein WL. Soluble dipeptidyl peptidase IV from terminal differentiated rat epidermal cells: purification and its activity on synthetic and natural peptides. Arch Biochem Biophys,1988,266:369-376.
[3] Drucker DJ,Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet,2006,368:1696-1705.
[4] Irie M,Suzuki N,Sohda T,et al. Hepatic expression of gammaglutamyl transpeptidase in the human liver of patients with alcoholic liver disease. Hepatol Res,2007,37:966-973.
[5] Yamabe T,Takakura K,Sugie K,et al. Induction of the 2B9 antigen/dipeptidyl peptidase IV/CD26 on human natural killer cells by IL-2,IL-12 or IL-15. Immunology,1997,91:151-158.
[6] Ohnuma K,Yamochi T,Uchiyama M. CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1. Proc Natl Acad Sci USA,2004,101:14186-14191.
[7] Ohnuma K,Uchiyama M,Yamochi T. Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. J Biol Chem,2007,282:10117-10131.
[8] Conarello SL,Li Z,Ronan J,et al. Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci USA,2003,100:6825-6830.
[9] Piazza GA,Callanan HM,Mowery J. Evidence for a role of dipeptidyl peptidase IV in fibronectin-mediated interactions of hepatocytes with extracellular matrix. Bio-chem J,1989,262: 327-334.
[10] Loster K,Zeilinger K,Schuppan D,et al. The cysteine-rich region of dipeptidyl peptidase IV（CD 26） is the collagen-binding site. Biochem Biophys Res Commun,1995,217:341-348.
[11] Inamoto T,YamochiT,Ohnuma K,et al. Anti-CD26 monoclonal antibody-mediated G1-S arrest of human renal clear cell carcinoma Caki2 is associated with retinoblastoma substrate dephosphorylation,cyclin-dependent kinase 2 reduction,p27（kip1） enhancement,and disruption of binding to the extracellular matrix. Clin Cancer Res,2006,12:3470-3477.
[12] Wesley UV,McGroarty M,Homoyouni A. Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway. Cancer Res,2005,65:1325-1334.
[13] Sato T,Yamochi T,Yamochi T. CD26 regulates p38 mitogen-activated protein kinase-dependent phosphorylation of integrin beta1,adhesion to extracellular matrix,and tumorigenicity of T-anaplastic large cell lymphoma Karpas 299. Cancer Res,2005,65:6950-6956.
[14] Matsumoto Y,Bishop GA,McCaughan GW. Altered zonal expression of the CD26 antigen （dipeptidyl peptidase IV） in human cirrhotic liver. Hepatology,1992,15:1048-1053.
[15] De Marco R,Locatelli F,Zoppini G,et al. Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study. Diabetes Care,1999,22:756-761.
[16] Williams I. Epidemiology of hepatitis C in the United States. Am J Med,1999,107:2S-9S.
[17] Caronia S,Taylor K,Pagliaro L,et al. Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology,1999,30:1059-1063.
[18] Rudoni S,Petit JM,Bour JB,et al. HCV infection and diabetes mellitus:influence of the use of finger stick devices on nosocomial transmission. Diabetes Metab,1999,25:502-505.
[19] Honeyman MC,Stone NL,Harrison LC. T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA2:potential for mimicry with rotavirus and other envirommental agents. Mol Med,1998,4:231-239.
[20] Strassburg CP,Obermayer-Straaub P,Manns MP. Autoimmunity in hepatitis C and D virus infection. J Viral Hepatitis,1996,3:49-59.
[21] Harman-Boehm I,Zingman L,Hilzenrat N. No evidence for anti-islet autoimmunity in diabetes mellitus associated with chronic hepatitis C infection （Letter）. Hepatology,1999,30:342.
[22] Sangiorgio L,Attardo T,Gangemi R,et al. Increased frequency of HCV and HBV infection in type 2 diabetic patients. Diabetes Res Clin Pract,2000,48:147-151.
[23] Betterle C,Fabris P,Zanchetta R,et al. Autoimmunity againts pancreatic islets and other tissues before and after interferon alpha therapy in patients with hepatitis C virus chronic infection. Diabetes Care,2000,23:1177-1181.
[24] Laskus T,Radkowski M,Wang LF,et al Search for hepatitis C virus extrahepatic replication sites in patients with acquired immunodeficiency syndrome:specific detection of negative-strand viral RNA in various tissues. Hepatology,1998,28:1398-1401.
[25] Grüngreiff K,Hebell T,Gutensohn K. Plasma concentrations of zinc,copper,interleukin-6 and interferon-γ,and plasma dipeptidyl peptidase IV activity in chronic hepatitis C. Mol Med Report,2009,2:63-68.
[26] Bonacini M,Govindarajan S,Kohla M. Intrahepatic lymphocyte phenotypes in hepatitis C virus infection:a comparison between cirrhotic and non-cirrhotic livers. Minerva Gastroenterol Dietol,2007,53:1-7.
[27] Shintani Y,Fujie H,Miyoshi H. Hepatitis C virus infection and diabetes:direct involvement of the virus in the development of insulin resistance. Gastroenterology,2004,126:840-848.
[28] Arase Y,Suzuki F,Kobayashi M. Efficacy and safety in sitagliptin therapy for diabetes complicated by chronic liver disease caused by hepatitis C virus. Hepatol Res,2011,41:524-529.
[29] Eguchi Y,Hyogo H,Ono M. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan:a multicenter large retrospective study. J Gastroenterol,2012,47:586-595.
[30] Takaki A,Kawai D,Yamamoto K. Molecular mechanisms and new treatment strategies for non-alcoholic steatohepatitis （NASH）. Int J Mol Sci,2014,15:7352-7379.
[31] Chalasani N,Guo X,Loomba R,et al. Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease. Gastroenterology,2010,139:1567-1576.
[32] Bhatt SP,Nigam P,Misra A,et al. Genetic variation in the patatin-like phospholipase domain-containing protein-3 （PNPLA-3） gene in Asian Indians with nonalcoholic fatty liver disease.Metab Syndr Relat Disord,2013,11:329-335.
[33] Balaban YH,Korkusuz P,Simsek H. Dipeptidyl peptidase IV （DDP IV） in NASH patients. Ann Hepatol,2007,6:242-250.
[34] Ben-Shlomo S,Zvibel I,Shnell M. Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase. J Hepatol,2011,54:1214-1223.
[35] Yilmaz Y,Yonal O,Deyneli O. Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis. Acta Gastroenterol Belg,2012,75:240-244.
[36] Aoe K,Amatya VJ,Fujimoto N. CD26 overexpression is associated with prolonged survival and enhanced chemosensitivity in malignant pleural mesothelioma. Clin Cancer Res,2012,18:1447-1456.
[37] Gaetaniello L,Fiore M,de Filippo S. Occupancy of dipeptidyl peptidase IV activates an associated tyrosine kinase and triggers an apoptotic signal in human hepatocarcinoma cells. Hepatology,1998,27:934-942.

What roles does dipeptidyl peptidase-4 play in chronic liver diseases?

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Wu Dan Ma Xiangying.. Insulin resistance,carotid atherosclerosis and left ventricular function in patients with NAFLD-induced liver cirrhosis [J]. Journal of Practical Hepatology, 2019, 22(6): 876-879.
[2]	Zhang Xu Lei, Yang Qingyu, Han Qiuyu, et al. Short-term efficacy of herbal medicine in treatment of patients with nonalcoholic fatty liver disease [J]. Journal of Practical Hepatology, 2019, 22(5): 660-663.
[3]	Xie Xiao, Liu Ting, Dong Zhixia, et al. Value of controlled attenuation parameter in diagnosis of individuals with liver steatosis by using Fibrotouch [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(4): 526-529.
[4]	Fu Liang, Wu Dongbing, Ji Xinzun. Application of ARFI quantification in the evaluation of liver injuries in patients with non-alcoholic fatty liver disease [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(3): 377-380.
[5]	Zhu Guangxi，Wen Liangzhi，Chen Dongfeng. Pathogenesis of non-alcoholic fatty liver disease-related hepatocellular carcinoma [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(3): 453-456.
[6]	Su Shuting, Zhong Yan, Mi Yuqiang.. Management of patients with non-alcoholic fatty liver disease [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(2): 293-296.
[7]	Zhang Feng, Yan Yan.. Implication of serum apolipoprotein B levels and its correlation with metabolic syndrome in checked-up individuals [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(1): 61-64.
[8]	Song Na, Liu Xiaoyan, Liu Chang, et al.. Changes of plasma thyrotropin levels in patients with nonalcoholic fatty liver disease and type 2 diabetes [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(1): 65-68.
[9]	Cui Qinghua, Tao Hong, Wang Xiaoyue, et al.. Changes of serum glycosylated hemoglobin level and cardiac functions in patients with non-alcoholic fatty liver disease [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(1): 69-72.
[10]	Hu Hulan, Zhu Mengfei, Shi Junping.. Non-alcoholic fatty liver disease with concurrent chronic hepatitis B: What’s the progress [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(1): 149-152.
[11]	Dong Xuelian, Zhang Wenjun.. Application of controlled attenuation parameter in screening individuals with risk of metabolic syndrome [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(6): 868-871.
[12]	Huang Faguang, Li Xiaocheng, Gong Jianping, et al.. Research on insulin resistance related protein molecules in human liver tissues by comprehensive gene expression profiling analysis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(6): 872-876.
[13]	Ge Jianxiang, Sun Yezi, Zhao Yun.. Application of entecavir in the treatment of patients with HBV-related cirrhosis complicated by hepatogenous diabetes and its influence on indexes of glucose metabolism [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(5): 677-680.
[14]	Liu Yanghe, Long Dengyi, Bei Zheng, et al. Efficacy of bacillus subtilis duplex and polyene phosphatidylcholine combination in treatments of patients with nonalcoholic fatty liver diseases [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(4): 573-576.
[15]	Xie Zhanfeng, Jia Jizhen, Zhao Shufang. Combination of notoginseng total saponin and silybin in treatment of patients with non-alcoholic fatty liver diseases [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(4): 623-624.