Study on the regulation and molecular mechanism of octreotide on human liver fibrosis
-
摘要: [目的]:通过探讨奥曲肽干预人肝星状细胞株LX-2后的细胞增殖和凋亡情况以及STAT3、SOCS3的表达水平,进一步研究奥曲肽对人肝纤维化进程可能的调控机制。[方法]体外培养LX-2,使用不同浓度的奥曲肽(10-3、10-4、10-5、10-6mmol/L)作用于LX-2 24 h后,采用MTT法和TUNEL荧光法分别检测LX-2的增殖和凋亡情况,采用免疫细胞化学法检测STAT3、SOCS3蛋白水平的表达,采用RT-PCR法检测STAT3和SOCS3 mRNA水平的表达。[结果]奥曲肽可以降低LX-2的增殖速度,并促进其凋亡;同时,奥曲肽能够下调STAT3、SOCS3在蛋白及mRNA水平的表达。[结论]奥曲肽可以通过抑制LX-2增殖、促进其凋亡从而延缓肝纤维化进展,并且该作用可能是通过抑制STAT3、SOCS3的表达实现的。Abstract: [Objective]To study the effect of octreotide on proliferation,apoptosis and the expression level of STAT3 and SOCS3 in hepatic stellate cells LX-2,further to discuss the possible regulation mechanism of octreotide on human hepatic fibrosis process.[Methods]LX-2 were cultured in vitro,and were intervened by different concentrations of octreotide(10-3,10-4,10-5,10-6mmol/L)for 24 h,proliferation and apoptosis of LX-2 were detected by MTT and TUNEL,the expression of STAT3 and SOCS3 protein were measured by immunocytochemistry,and the expression of STAT3 and SOCS3 mRNA levels were detected by RT-PCR.[Results]octreotide can reduce the proliferation of LX-2,and promote apoptosis.At the same time,octreotide can enhance the proliferation of SOCS3 and STAT3 at mRNA and protein level.[Conclusion]Octreotide may inhibit LX-2 proliferation,and promote apoptosis to delay the progress of liver fibrosis,and the effect may be through inhibition the expression of STAT3 and SOCS3.
-
Key words:
- octreotide /
- human hepatic stellate cells /
- proliferation /
- apoptosis /
- STAT3 /
- SOCS3
-
-
[1] 石磊, 秦恩强, 贾雅丽, 等.肝星状细胞中表皮形态发生素表达调控机制及其作用研究[J].生物化学与生物物理进展, 2016, 43 (5):506-513.
[2] 杨文燕, 戴强.长效奥曲肽对肝纤维化大鼠IL-6、IL-8的影响[J].重庆医学, 2009, 38 (3):293-294+296+379+244.
[3] Mughal T I, Girnius S, Rosen S T, et al.Emerging therapeutic paradigms to target the dysregulated Janus kinase/signal transducer and activator of transcription pathway in hematological malignancies[J].Leukemia&lymphoma, 2014, 55 (9):1968-1979.
[4] Block E T, Cronstein B N.Interferon-gamma inhibits adenosine A2 A receptor function in hepatic stellate cells by STAT1-mediated repression of adenylyl cyclase[J].Int J Interferon, Cytokine Mediat Res, 2010 (2):113-113.
[5] Nobori K, Munehisa Y.Intracellular signaling pathways for cardiac hypertrophy:ERK, JAK-STAT, S6kinase[J].Nihon Rinsho, 2007, 65 (4):196-200.
[6] Rehermann B.Hepatitis C virus versus innate and adaptive immune responses:a tale of coevolution and coexistence[J].J Clin Invest, 2009, 119 (7):1745-1754.
[7] Pascarella S, Clément S, Dill M T, et al.Intrahepatic mRNA levels of SOCS1and SOCS3are associated with cirrhosis but do not predict virological response to therapy in chronic hepatitis C[J].Liver Int, 2013, 33 (1):94-103.
[8] Culig Z.Suppressors of cytokine signalling-3and-1in human carcinogenesis[J].Front Biosci (Schol Ed), 2013, 5 (1):277-283.
[9] 杨卫富, 李德春.Stat3与肿瘤的关系研究进展[J].蚌埠医学院学报, 2013, 38 (2):234-236.
[10] Xu MY, Hu JJ, Shen J, et al.Stat3signaling activation crosslinking of TGF-beta1in hepatic stellate cell exacerbates liver injury and fibrosis[J].Biochim Biophys Acta, 2014, 1842 (11):2237-2245.
[11] Lin S, Saxena NK, Ding X, et al.Leptin increases tissue inhibitor of metallopro-teinase I (TIMP-1) gene expression by a specific-ity protein 1/signal transducer and activator oftranscription 3mechanism[J].Mol Endocrinol, 2006, 20 (12):3376-3388.
[12] Plum W, Tschaharganeh DF, Kroy DC, et al.Lack of glycoprotein 130/signal transducer and activator of transcription 3-mediated signaling in hepatocytes enhances chronic liver injury and fibrosis progression in a model of sclerosing cholangitis[J].Am J Pathol, 2010, 176 (5):2236-2246.
[13] Mahony R, Ahmed S, Diskin C, et al.SOCS3revisited:a broad regulator of disease, now ready for therapeutic use?[J].Cellular and Molecular Life Sciences, 2016, 73 (17):3323-3336.
[14] Babon J J, Nicola N A.The biology and mechanism of action of suppressor of cytokine signaling 3[J].Growth Factors, 2012, 30 (4):207-219.
[15] Li Y, Han M F, Li W N, et al.SOCS3expression correlates with severity of inflammation in mouse hepatitis virus strain 3-induced acute liver failure and HBVACLF[J].J Huazhong Univ Sci Technolog Med Sci, 2014, 34 (3):348-353.
[16] Wang B, Zhang X H, Yang M F, et al.Expression and significance of SOCS3in liver tissue of rats with severe acute pancreatitis complicated by liver injury[J].The People'sLiberat Army Med J, 2012, 37 (11):1036-1039.
[17] 刘青娟, 邢玲玲, 郝军, 等.SOCS-3对OSM诱导的肾小管上皮细胞转分化的影响[J].临床与实验病理学杂志, 2013, 29 (11):1165-1167, 1171.
[18] da Silva CG, Studer P, Skroch M, et al.A20promotes liver regeneration by decreasing SOCS3expression to enhance IL-6/STAT3proliferative signals[J].Hepatology, 2013, 57 (5):2014-2025.
-
计量
- 文章访问数: 197
- PDF下载数: 83
- 施引文献: 0