Toll样受体信号通路在肝纤维化机制中的作用_West China Medical Journal

Authors：

 文皑巍 ,  曹文富

重庆医科大学附属第一医院中西医结合科（重庆 400042）;

Corresponding author：

曹文富, Email: 13883658367@163.com

Keywords：

肝纤维化; Toll样受体信号通路; 机制; 进展

DOI：

10.7507/1002-0179.20150222

Video：

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肝纤维化是肝脏损害发展到一定程度后的病理生理表现，其发病机制目前尚未完全明了，治疗方法也极为有限。Toll样受体（TLR）作为最重要的一种模式识别受体，在机体固有免疫及获得性免疫应答过程中的重要性已得到论证，近年其与肝纤维化病理生理过程之间的联系正得到大量研究。TLR通过识别外源性或内源性配体及接受其他因子对其自身表达的调节而影响下游多种细胞因子表达，在肝纤维化病理生理过程中发挥了重要作用。同时，参与这一过程的部分关键因子也为临床干预治疗提供了靶点，这有利于研究既有药物在肝纤维化中的应用及新药开发，进而为肝纤维化控制指明一个新方向。现就TLR信号通路在肝纤维化机制中的作用作一综述。

Citation： 文皑巍, 曹文富. Toll样受体信号通路在肝纤维化机制中的作用. West China Medical Journal, 2015, 30(4): 779-782. doi: 10.7507/1002-0179.20150222 Copy

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16.	Shirai Y, Yoshiji H, Noguchi R, et al. Cross talk between toll-like receptor-4 signaling and angiotensin-Ⅱ in liver fibrosis development in the rat model of non-alcoholic steatohepatitis[J]. J Gastroenterol Hepatol, 2013, 28(4):723-730.
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23.	Abu-Tair L, Axelrod JH, Doron S, et al. Natural killer cell-dependent anti-fibrotic pathway in liver injury via Toll-like receptor-9[J]. PLoS One, 2013, 8(12):e82571.
24.	Wang B, Trippler M, Pei R, et al. Toll-like receptor activated human and murine hepatic stellate cells are potent regulators of hepatitis C virus replication[J]. J Hepatol, 2009, 51(6):1037-1045.
25.	Paik YH, Lee KS, Lee HJ, et al. Hepatic stellate cells primed with cytokines upregulate inflammation in response to peptidoglycan or lipoteichoic acid[J]. Lab Invest, 2006, 86(7):676-686.

1. Friedman SL. Evolving challenges in hepatic fibrosis[J]. Nat Rev Gastroenterol Hepatol, 2010, 7(8):425-436.
2. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity[J]. Cell, 2006, 124(4):783-801.
3. Takeuchi O, Akira S. Pattern recognition receptors and inflammation[J]. Cell, 2010, 140(6):805-820.
4. Seki E, De Minicis S, Osterreicher CH, et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis[J]. Nat Med, 2007, 13(11):1324-1332.
5. Liu C, Chen X, Yang L, et al. Transcriptional repression of the transforming growth factor β (TGF-β) pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) by nuclear factor κB (NF-κB) p50 enhances TGF-β signaling in hepatic stellate cells[J]. J Biol Chem, 2014, 289(10):7082-7091.
6. Wiest R, Lawson M, Geuking M. Pathological bacterial translocation in liver cirrhosis[J]. J Hepatol, 2014, 60(1):197-209.
7. Zhu Q, Zou L, Jagavelu K, et al. Intestinal decontamination inhibits TLR4 dependent fibronectin-mediated cross-talk between stellate cells and endothelial cells in liver fibrosis in mice[J]. J Hepatol, 2012, 56 (4):893-899.
8. Zhao WX, Wang L, Yang JL, et al. Caffeic acid phenethyl ester attenuates pro-inflammatory and fibrogenic phenotypes of LPS-stimulated hepatic stellate cells through the inhibition of NF-κB signaling[J]. Int J Mol Med, 2014, 33(3):687-694.
9. Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity[J]. Cell, 2010, 140(6):798-804.
10. Chen R, Hou W, Zhang Q, et al. Emerging role of high-mobility group box 1 (HMGB1)in liver diseases[J]. Mol Med, 2013(19):357-366.
11. Li L, Chen L, Hu L, et al. Nuclear factor high-mobility group box1 mediating the activation of Toll-like receptor 4 signaling in hepatocytes in the early stage of nonalcoholic fatty liver disease in mice[J]. Hepatology, 2011, 54(5):1620-1630.
12. Ge WS, Wu JX, Fan JG, et al. Inhibition of high-mobility group box 1 expression by siRNA in rat hepatic stellate cells[J]. World J Gastroenterol, 2011, 17(36):4090-4098.
13. Zhang Z, Lin C, Peng L. High mobility group box 1 activates Toll like receptor 4 signaling in hepatic stellate cells[J]. Life Sci, 2012, 91(5/6):207-212.
14. Wang FP, Li L, Li J, et al. High mobility group box-1 promotes the proliferation and migration of hepatic stellate cells via TLR4-dependent signal pathways of P13K/Akt and JNK[J]. PLoS One, 2013, 8(5):e64373.
15. Yoshiji H, Kuriyama S, Fukui H. Angiotensin-Ⅰ-converting enzyme inhibitors may be an alternative anti-angiogenic strategy in the treatment of liver fibrosis and hepatocellular carcinoma. Possible role of vascular endothelial growth factor[J]. Tumour Biol, 2002, 23(6):348-356.
16. Shirai Y, Yoshiji H, Noguchi R, et al. Cross talk between toll-like receptor-4 signaling and angiotensin-Ⅱ in liver fibrosis development in the rat model of non-alcoholic steatohepatitis[J]. J Gastroenterol Hepatol, 2013, 28(4):723-730.
17. Li YS, Ni SY, Meng Y, et al. Angiotensin Ⅱ facilitates fibrogenic effect of TGF-β1 through enhancing the down-regulation of BAMBI caused by LPS:a new pro-fibrotic mechanism of angiotensin Ⅱ[J]. PLoS One, 2013, 8(10):e76289.
18. Shahid SM, Fatima SN, Mahboob T. Angiotensin converting enzyme (ACE) gene expression in experimentally induced liver cirrhosis in rats[J]. Pak J Pharm Sci, 2013, 26(5):853-857.
19. Attia YM, Elalkamy EF, Hammam OA, et al. Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection[J]. Parasit Vectors, 2013(6):199.
20. Roh YS, Seki E. Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis[J]. J Gastroenterol Hepatol, 2013, 28(Suppl 1):38-42.
21. Watanabe A, Hashmi A, Gomes DA, et al. Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9[J]. Hepatology, 2007, 46(5):1509-1518.
22. Miura K, Kodama Y, Inokuchi S, et al. Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice[J]. Gastroenterology, 2010, 139(1):323-334.
23. Abu-Tair L, Axelrod JH, Doron S, et al. Natural killer cell-dependent anti-fibrotic pathway in liver injury via Toll-like receptor-9[J]. PLoS One, 2013, 8(12):e82571.
24. Wang B, Trippler M, Pei R, et al. Toll-like receptor activated human and murine hepatic stellate cells are potent regulators of hepatitis C virus replication[J]. J Hepatol, 2009, 51(6):1037-1045.
25. Paik YH, Lee KS, Lee HJ, et al. Hepatic stellate cells primed with cytokines upregulate inflammation in response to peptidoglycan or lipoteichoic acid[J]. Lab Invest, 2006, 86(7):676-686.

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West China Medical Journal

Toll样受体信号通路在肝纤维化机制中的作用

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