TNFα/NF-κB信号通路调控非酒精性脂肪性肝病的研究现状

孙婷婷; 李京涛; 魏海梁; 闫曙光; 李倩; 郭英君; 常占杰

doi:10.3969/j.issn.1001-5256.2019.09.047

TNFα/NF-κB信号通路调控非酒精性脂肪性肝病的研究现状

DOI: 10.3969/j.issn.1001-5256.2019.09.047

1. 陕西中医药大学
2. 陕西中医药大学附属医院
3. 宁夏回族自治区人民医院

基金项目:

国家自然科学基金(81603612)；陕西省科技厅科研基金(2016SF-234,2018KJXX-093)；陕西省教育厅基金(16JK1212)；陕西省中管局基金(15-JC008)；宁夏回族自治区自然科学基金(NZ17278)；陕西中医药大学学科创新团队建设项目(2019-YL05)；银川市2017年科技攻关项目；

详细信息

中图分类号: R575.5
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出版历程
- 收稿日期: 2019-04-09
- 出版日期: 2019-09-20

Research advances in the role of the TNF-α/NF-κB signaling pathway in the regulation of nonalcoholic fatty liver disease

Shaanxi University of Chinese Medicine

Research funding:

摘要

摘要: TNFα可诱导肝脏炎症反应,促进肝细胞变性、坏死。核因子-κB（NF-κB）作为重要的转录调控因子,在非酒精性脂肪性肝病（NAFLD）中起着促进肝脏脂肪变性的重要作用。TNFα/NF-κB信号通路在各种信号刺激的条件下促进了NAFLD的发展。主要讨论了TNFα/NF-κB信号通路在NAFLD中的作用机制,旨在为NAFLD患者提供新的治疗靶点。
- 非酒精性脂肪性肝病 /
- 肿瘤坏死因子α /
- NF-κB
Abstract: Tumor necrosis factor-α ( TNF-α) can induce liver inflammation and promote hepatocyte degeneration and necrosis, and as an important transcription regulator, nuclear factor-κB ( NF-κB) can promote hepatic steatosis in nonalcoholic fatty liver disease ( NAFLD) .The TNF-α/NF-κB signaling pathway promotes the development of NAFLD under the stimulation of various signals. This article discusses the mechanism of action of the TNF-α/NF-κB signaling pathway in NAFLD, so as to provide new therapeutic targets for patients with NAFLD.
- nonalcoholic fatty liver disease /
- tumor necrosis factor-alpha /
- NF-kappa B

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参考文献(33)

[1] National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association;Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease:A 2018 update[J]. J Clin Hepatol, 2018, 34 (5) :947-957. (in Chinese) 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会.非酒精性脂肪性肝病防治指南 (2018年更新版) [J].临床肝胆病杂志, 2018, 34 (5) :947-957.

[2] LONARDO A, BALLESTRI S, MARCHESINI G, et al. Nonalcoholic fatty liver disease:A precursor of the metabolic syndrome[J]. Dig Liver Dis, 2015, 47 (3) :1-10.

[3] TILG H, MOSCHEN AR, RODEN M. NAFLD and diabetes mellitus[J]. Nat Rev Gastroenterol Hepatol, 2017, 14 (1) :32-42.

[4] WONG RJ, AGUILAR M, CHEUNG R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States[J]. Gastroenterology, 2015, 148 (3) :547-555.

[5] CHEN ZG, YU R, XIONG Y, et al. A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease[J]. Lipids Health Dis, 2017, 16 (1) :203-211.

[6] CATHERINE D, MELANIE G, ELISABETH L, et al. The TNF family of ligands and receptors:Communication modules in the immune system and beyond[J]. Physiol Rev, 2019, 99 (1) :115-160.

[7] HEHLGANS T, PFEFFER K. The intriguing biology of the tumour necrosisfactor/tumour necrosis factor receptor superfamily:Players, rules and the games[J]. Immunology, 2005, 115 (1) :1-20.

[8] VARFOLOMEEV EE, ASHKENAZI A. Tumor necrosis factor:An apoptosis JuNKie[J]. Cell, 2004, 116 (4) :491-497.

[9] KERN L, MITTENBUHLER MJ, VESTING AJ, et al. Obesityinduced TNF-αand IL-6 signaling:The missing link between obesity and inflammation-driven liver and colorectal cancers[J]. Cancers (Basel) , 2018, 11 (1) :1-21.

[10] ZHANG Q, LENARDO MJ, BALTIMORE D, et al. 30 years of NF-κB:A blossoming of relevance to human pathobiology[J]. Cell, 2017, 168 (1-2) :37-57.

[11] LIN QX. The effects of gingko flavonoid on the expression of NF-κBp65 in mice with non-alcoholic fatty liver disease[D].Guilin:Guilin Medical University, 2014. (in Chinese) 林秋香.银杏黄酮对非酒精性脂肪肝小鼠肝脏NF-κBp65的影响[D].桂林:桂林医学院, 2014.

[12] PASCHETTA E, BELCI P, ALISI A, et al. OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver disease[J]. Mediators Inflamm, 2015, 2015:815721.

[13] QIN Y, ZHAO D, ZHOU HG, et al. Apigenin inhibits NF-κB and snail signaling, emt and metastasis in human hepatocellular carcinoma[J]. Oncotarget, 2016, 7 (27) :41421-41431.

[14] ANTHONY NG, BAIGET J, BERRETTA G, et al. Inhibitory kappa B kinaseα (IKKα) inhibitors that recapitulate their selectivity in cells against isoform-related biomarkers[J]. J Med Chem, 2017, 60 (16) :7043-7066.

[15] CHEN YZ, CHEN CL, HONG Y, et al. Research advances in the pathogenesis and risk factors of non-obese non-alcoholic fatty liver fibrosis and liver cirrhosis[J]. J Clin Hepatol, 2018, 34 (10) :2227-2231. (in Chinese) 陈艳珍, 陈成良, 洪宇, 等.非肥胖型非酒精性脂肪性肝纤维化、肝硬化的发病机制及危险因素[J].临床肝胆病杂志, 2018, 34 (10) :2227-2231.

[16] LOPETUSO LR, MOCCI G, MARZO M, et al. Harmful effects and potential benefits of anti-tumor necrosis factor (TNF) -αon the liver[J]. Int J Mol Sci, 2018, 19 (8) :1-22.

[17] ZHANG ZL, HUANG YS, FAN YD, et al. Effect of Xuezhikang on hepatitis and oxidative stress in rats with nonalcoholic fatty liver disease[J]. Chin J Med Offic, 2018, 46 (6) :605-609. (in Chinese) 张子龙, 黄樱硕, 范煜东, 等.血脂康对非酒精性脂肪性肝病大鼠肝炎症及氧化应激影响[J].临床军医杂志, 2018, 46 (6) :605-609.

[18] YANG R, GUAN MJ, ZHAO N, et al. Roles of extrahepatic lipolysis and the disturbance of hepatic fatty acid metabolism in TNF-α-induced hepatic steatosis[J]. Toxicology, 2019, 411:172-180.

[19] KADASHEV IP. NF-kB activation as a molecular basis of pathological process by metabolic syndrome[J]. Fiziol Zh, 2012, 58 (1) :93-101.

[20] SHIH RH, WANG CY, YANG CM. NF-kappaB signaling pathways in neurological inflammation:A mini review[J].Front Mol Neurosci, 2015, 8:77.

[21] LI X, MENG Y, YANG XS, et al. Effect of N-acetylcysteine on nuclear factor-κB binding activity and expression of cyclooxygenase-2 in hepatic stellate cell[J]. Chin J Dig, 2005, 25 (2) :22-25. (in Chinese) 李旭, 孟莹, 杨希山, 等. N-乙酰半胱氨酸对肝星状细胞核因子κB的影响[J].中华消化杂志, 2005, 25 (2) :22-25.

[22] WREE A, BRODERICK L, CANBAY A, et al. From NAFLD to NASH to cirrhosis-new insights into disease mechanisms[J].Nat Rev Gastroenterol Hepatol, 2013, 10 (11) :627-636.

[23] TRAUSSNIGG S, KIENBACHER C, HALILBASIC E, et al. Challenges and management of liver cirrhosis:Practical issues in the therapy of patients with cirrhosis due to NAFLD and NASH[J].Dig Dis, 2015, 33 (4) :598-607.

[24] CAI J, ZHANG XJ, LI H. The Role of innate immune cells in nonalcoholic steatohepatitis[J]. Hepatology, 2019.[Epub ahead of print]

[25] YAO XR, XIA F, TANG WJ, et al. Effect of Hugan Qingzhi tablets on AMPK pathway activation and NF-κB-p65 protein expression in the liver of rats with nonalcoholic fatty liver disease[J]. J South Med Univ, 2017, 37 (1) :56-62. (in Chinese) 姚笑睿, 夏凡, 唐外姣, 等.护肝清脂片对非酒精性脂肪肝大鼠肝脏中AMPK通路激活及NF-κB-p65蛋白的影响[J].南方医科大学学报, 2017, 37 (1) :56-62.

[26] ZHANG T, HU J, WANG X, et al. MicroRNA-378 promotes hepatic inflammation and fibrosis via modulation of the NF-κB-TNFαpathway[J]. J Hepatol, 2019, 70 (1) :87-96.

[27] LYONS CL, ROCHE HM. Nutritional modulation of AMPK-impact upon metabolic-inflammation[J]. Int J Mol Sci, 2018, 19 (10) :3092-3107.

[28] JI K, SUN X, LIU Y, et al. Regulation of apoptosis and radiation sensitization in lung cancer cells via the Sirt1/NF-κB/Smac pathway[J]. Cell Physiol Biochem, 2018, 48 (1) :304-316.

[29] DOU X, LI S, HU L, et al. Glutathione disulfide sensitizes hepatocytes to TNFα-mediated cytotoxicity via IKK-βS-glutathionylation:A potential mechanism underlying non-alcoholic fatty liver disease[J]. Exp Mol Med, 2018, 50 (4) :7-23.

[30] JIANG H, GUAN Q, XIAO Y, et al. Strontium alleviates endoplasmic reticulum stress in a nonalcoholic fatty liver disease model[J]. J Med Food, 2018.[Epub ahead of print]

[31] MITRA S, RYOO HD. The unfolded protein response in metazoan development[J]. J Cell Sci, 2019, 132 (5) :1-9.

[32] WALTER P, RON D. The unfolded protein response:From stress pathway to Homeos-tatic regulation[J]. Science, 2011, 334 (6059) :1081-1086.

[33] NAKAJIMA S, KITAMURA M. Bidirectional regulation of NF-κB by reactive oxygen species:A role of unfolded protein response[J]. Free Radic Biol Med, 2013, 65:162-174.

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