肝纤维化治疗新策略

钟巍; 谢渭芬

肝纤维化治疗新策略

钟巍,
谢渭芬

第二军医大学附属长征医院消化内科

详细信息

中图分类号: R575.2
计量
- 文章访问数: 3337
- HTML全文浏览量: 16
- PDF下载量: 1442
- 被引次数: 0
出版历程
- 出版日期: 2011-03-20

New strategy for the treatment of hepatic fibrosis

摘要

摘要: 肝纤维化是各种慢性肝病共有的病理改变,逆转肝纤维化可阻止大多数慢性肝病进展。肝星状细胞(HSC)活化是肝纤维化发生的中心环节,故传统治疗策略大多以HSC为治疗靶点,并在动物实验取得良好疗效。但最近研究发现活化HSC也可促进肝细胞再生和肝脏损伤修复。肝细胞核因子是一组对肝细胞分化和功能维持起关键作用的转录因子,既可减少细胞外基质(ECM)分泌,又可促进肝细胞再生,保护肝细胞功能。促进肝细胞核因子表达是治疗肝纤维化更为理想的策略。
- 肝硬化
Abstract: Hepatic fibrosis is the common pathological change of chronic liver diseases, and reversal of fibrosis can prevent the progression of most chronic liver diseases.The activation of hepatic stellate cells (HSCs) is considered as the central event of hepatic fibrosis, thus the traditional therapy for hepatic fibrosis was targeting to HSC and have achieved substantial efficacy in animal experiments.However, recent studies have indicated that the activation of HSCs also contributes to the hepatocyte proliferation and live regeneration.Hepatocyte nuclear factors (HNFs) consist of a group of transcription factors, which are critical for the hepatocyte differentiation and functional maintenance.Forced expression of HNFs could reduce the secretion of ECM, promote hepatocyte regeneration and improve liver function.Therefore, upregulation of HNFs presents as an ideal strategy for the treatment of hepatic fibrosis.
- liver cirrhosis

HTML全文

参考文献(28)

[1]Bataller R, Brenner DA.Liver fibrosis[J].J Clin Invest, 2005, 115 (2) :209-218.

[2]Poynard T, Bedossa P, Opolon P.Natural history of liver fibrosis progression in patients with chronic hepatitis C.The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups[J].Lancet, 1997, 349 (9055) :825-832.

[3]Boccato S, Pistis R, Noventa F, et al.Fibrosis progression in initially mild chronic hepatitis C[J].J Viral Hepat, 2006, 13 (5) :297-302.

[4]Friedman SL.Hepatic stellate cells[J].Prog Liver Dis, 1996, 14:101-130.

[5]Friedman SL, Roll FJ, Boyles J, et al.Hepatic lipocytes:the principal collagen-producing cells of normal rat liver[J].Proc Natl Acad Sci U S A, 1985, 82 (24) :8681-8685.

[6]Friedman SL.Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury[J].J Biol Chem, 2000, 275 (4) :2247-2250.

[7]Friedman SL.Hepatic stellate cells:protean, multifunctional, and enigmatic cells of the liver[J].Physiol Rev, 2008, 88 (1) :125-172.

[8]谢渭芬.肝纤维化治疗策略探讨[J].中华消化杂志, 2004, 24 (10) :577-578.

[9]Zhong W, Shen WF, Ning BF, et al.Inhibition of extracellular signal-regulated kinase 1 by adenovirus mediated siRNA attenuates hepatic fibrosis in rats[J].Hepatology, 2009, 50 (5) :1524-1536.

[10]Hu PF, Chen H, Zhong W, et al.Adenovirus-mediated transfer of siRNA against PAI-1 mRNA ameliorates hepatic fibrosis in rats[J].J Hepatol, 2009, 51 (1) :102-113.

[11]Chen SW, Chen YX, Zhang XR, et al.Targeted Inhibition of platelet-derived growth factor receptorβsubunit in hepatic stellate cells ameliorates hepatic fibrosis in rats[J].Gene Therapy, 2008, 15 (21) :1424-1435.

[12]Passino MA, Adams RA, Sikorski SL, et al.Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR[J].Science, 2007, 315 (5820) :1853-1856.

[13]Benten D, Kumaran V, Joseph B, et al.Hepatocyte transplantation activates hepatic stellate cells with beneficial modulation of cell engraftment in the rat[J].Hepatology, 2005, 42 (5) :1072-1081.

[14]Kalinichenko VV, Bhattacharyya D, Zhou Y, et al.Foxf1+/-mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury[J].Hepatology, 2003, 37 (1) :107-117.

[15]Lorenzini S, Bird TG, Boulter L, et al.Characterisation of a ste-reotypical cellularand extracellular adult liver progenitor cell niche in rodents and diseased human liver[J].Gut, 2010, 59 (5) :645-654.

[16]Soto-Gutierrez A, Kobayashi N, Rivas-Carrillo JD, et al.Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes[J].Nat Biotechnol, 2006, 24 (11) :1412-1419.

[17] Deng X, Chen YX, Zhang X, et al.Hepatic stellate cells modulate the differentiation of bone marrow mesenchymal stem cells into hepatocyte-like cells[J].J Cell Physiol, 2008, 217 (1) :138-144.

[18]Pintilie DG, Shupe TD, Oh SH, et al.Hepatic stellate cells'involvement in progenitor-mediated liver regeneration[J].Lab Invest, 2010, 90 (8) :1199-1208.

[19]Kordes C, Sawitza I, Muller-Marbach A, et al.CD133+hepatic stellate cells are progenitor cells[J].Biochem Biophys Res Commun, 2007, 352 (2) :410-417.

[20]Yang L, Jung Y, Omenetti A, et al.Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers[J].Stem Cells, 2008, 26 (8) :2104-2113.:

[21]Odom DT, Zizlsperger N, Gordon DB, et al.Control of¨pancreas and liver gene expression by HNF transcription factors[J].Science, 2004, 303 (5662) :1378-1381.

[22]Parviz F, Matullo C, Garrison WD, et al.Hepatocyte nuclear factor 4αcontrols the development of a hepatic epithelium and liver morphogenesis[J].Nat Genet, 2003, 34 (3) :292-296.

[23]Li J, Ning G, Duncan SA.Mammalian hepatocyte differentiation requires the transcription factor HNF-4a[J].Genes Dev, 2000, 14 (4) :464-474.

[24]Hayhurst GP, Lee, Lambert G, et al.Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis[J].Mol Cell Biol, 2001, 21 (4) :1393-1403.

[25]Yin C, Lin Y, Zhang X, et al.Differentiation Therapy of Hepatocellular Carcinoma in Mice with Recombinant Adenovirus Carrying Hepatocyte Nuclear Factor-4αGene[J].Hepatology, 2008, 48 (5) :1528-1539.

[26]Yue HY, Yin C, Hou JL, et al.Hepatocyte nuclear factor 4αattenuates hepatic fibrosis in rats[J].Gut, 2010, 59 (2) :236-246.

[27]Ning BF, Ding J, Yin C, et al.Hepatocyte nuclear factor 4 alpha suppresses the development of hepatocellular carcinoma[J].Cancer Res, 2010, 70 (19) :7640-7651.

[28]Odom DT, Zizlsperger N, Gordon DB, et al.Control of pancreas and liver gene expression by HNF transcription factors[J].Science, 2004, 303 (5662) :1378-1381.

施引文献

资源附件(0)

访问统计