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肝星状细胞的活化机制—探寻肝纤维化新的诊断指标和治疗靶点

姜娜 平键 徐列明

引用本文:
Citation:

肝星状细胞的活化机制—探寻肝纤维化新的诊断指标和治疗靶点

DOI: 10.3969/j.issn.1001-5256.2019.03.042
基金项目: 

国家自然科学基金资助项目(81373859); 

详细信息
  • 中图分类号: R575.2

Mechanism of the activation of hepatic stellate cells:An exploration of new diagnostic markers and therapeutic targets for liver fibrosis

Research funding: 

 

  • 摘要: 肝纤维化的形成机制复杂,目前主流研究依然围绕肝星状细胞(HSC)开展,并发现许多促进HSC活化的刺激因子和调节通路。对影响HSC的几种主要细胞因子和过氧化物酶体增殖物激活受体γ相关近期研究结果以及近年的研究热点——小RNA、长非编码RNA、外泌体等与HSC活化的关系进行综述,旨在介绍治疗肝纤维化的潜在新靶点和非侵入性肝病诊断的新检测指标,提出将作用于HSC活化的不同靶点的化学药物或中药成分合理组成复方,以期在肝纤维化治疗学上有所突破的观点。

     

  • [1] CARSON JP, RAMM GA, ROBINSON MW, et al. Schistosome-induced fibrotic disease:The role of hepatic stellate cells[J]. Trends Parasitol, 2018, 34 (6) :524-540.
    [2] JUNG YK, YIM HJ. Reversal of liver cirrhosis:current evidenceand expectations[J]. Korean J Intern Med, 2017, 32 (2) :213-228.
    [3] TSUCHIDA T, FRIEDMAN SL. Mechanisms of hepatic stellatecell activation[J]. Nat Rev Gastroenterol Hepatol, 2017, 14 (7) :397-411.
    [4] WAKE K.“Sternzellen”in the liver:Perisinusoidal cells withspecial reference to storage of vitamin A[J]. Am J Anat, 1971, 132 (4) :429-462.
    [5] MEDERACKE I, DAPITO DH, AFFS, et al. High-yield andhigh-purity isolation of hepatic stellate cells from normal andfibrotic mouse livers[J]. Nat Protoc, 2015, 10 (2) :305-315.
    [6] LEE YA, WALLACE MC, FRIEDMAN SL. Pathobiology of liverfibrosis:A translational success story[J]. Gut, 2015, 64 (5) :830-841.
    [7] UENO T, SATA M, SAKATA R, et al. Hepatic stellate cellsand intralobular innervation in human liver cirrhosis[J]. HumPathol, 1997, 28 (8) :953-959.
    [8] HIGASHI T, FRIEDMAN SL, HOSHIDA Y. Hepatic stellate cells askey target in liver fibrosis[J]. Adv Drug Deliv Rev, 2017, 121:27-42.
    [9] KATZ LH, LIKHTER M, JOGUNOORI W, et al. TGFβsignalingin liver and gastrointestinal cancers[J]. Cancer Lett, 2016, 379 (2) :166-172.
    [10] LILIANA A, JEFFREY LW. Smads as transcriptional co-mod-ulators[J]. Curr Opin Cell Biol, 2000, 12 (2) :235-243.
    [11] CHEN J, KATZ LH, MUNOZ NM, et al. Vitamin D deficiencypromotes liver tumor growth in transforming growth factor-be-ta/Smad3-deficient mice through Wnt and Toll-like receptor7 pathway modulation[J]. Sci Rep, 2016, 6:30217.
    [12] LI XF, CHEN H, YI ZJ, et al. Imidazoline I2 receptor inhibitoridazoxan regulates the progression of hepatic fibrosis via AktNrf2 Smad2/3 signaling pathway[J]. Oncotarget, 2017, 8 (13) :21015-21030.
    [13] LI HY, JU D, ZHANG DW, et al. Activation of TGF-beta1-CD147 positive feedback loop in hepatic stellate cells pro-motes liver fibrosis[J]. Sci Rep, 2015, 5:16552.
    [14] CAI X, LI Z, ZHANG Q, et al. CXCL6-EGFR-inducedKupffer cells secrete TGF-beta1 promoting hepatic stellatecell activation via the SMAD2/BRD4/C-MYC/EZH2 pathwayin liver fibrosis[J]. J Cell Mol Med, 2018, 22 (10) :5050-5061.
    [15] ROSKOSKI R. The role of small molecule platelet-derived growthfactor receptor (PDGFR) inhibitors in the treatment of neoplasticdisorders[J]. Pharmacol Res, 2018, 129:65-83.
    [16] DING Q, LI Z, LIU B, et al. Propranolol prevents liver cirrhosisby inhibiting hepatic stellate cell activation mediated by thePDGFR/Akt pathway[J]. Hum Pathol, 2018, 76:37-46.
    [17] KOSTALLARI E, HIRSOVA P, PRASNICKA A, et al. Hepaticstellate cell-derived PDGFR alpha-enriched extracellularvesicles promote liver fibrosis in mice through SHP2[J]. Hep-atology, 2018, 68 (1) :333-348.
    [18] YANG L, KWON J, POPOV Y, et al. Vascular endothelialgrowth factor promotes fibrosis resolution and repair in mice[J]. Gastroenterology, 2014, 146 (5) :1339-1350. e1.
    [19] PETROSINO JM, LEASK A, ACCORNERO F. Genetic manipu-lation of CCN2/CTGF unveils cell-specific ECM-remodelingeffects in injured skeletal muscle[J]. FASEB J, 2018.[Epubahead of print]
    [20] HUANG G, BRIGSTOCK DR. Regulation of hepatic stellatecells by connective tissue growth factor[J]. Front Biosci, 2015, 17:2495-2507.
    [21] CHEN L, CHEN R, VELAZQUEZ VM, et al. Fibrogenic signa-ling is suppressed in hepatic stellate cells through targeting ofconnective tissue growth factor (CCN2) by cellular or exosom-al microRNA-199a-5p[J]. Am J Pathol, 2016, 186 (11) :2921-2933.
    [22] HAZRA S, XIONG S, WANG J, et al. Peroxisome proliferator-activated receptor gamma induces a phenotypic switch fromactivated to quiescent hepatic stellate cells[J]. J Biol Chem, 2004, 279 (12) :11392-11401.
    [23] MORAN-SALVADOR E, TITOS E, RIUS B, et al. Cell-specificPPARgamma deficiency establishes anti-inflammatory and anti-fibrogenic properties for this nuclear receptor in non-parenchy-mal liver cells[J]. J Hepatol, 2013, 59 (5) :1045-1053.
    [24] IWAISAKO K, HAIMERL M, PAIK YH, et al. Protection from liv-er fibrosis by a peroxisome proliferator-activated receptordelta agonist[J]. Proc Natl Acad Sci U S A, 2012, 109 (21) :e1369-e1376.
    [25] ZHANG F, LU S, HE J, et al. Ligand activation of PPARγbyligustrazine suppresses pericyte functions of hepatic stellatecells via SMRT-mediated transrepression of HIF-1α[J].Theranostics, 2018, 8 (3) :610-626.
    [26] RATZIU V, HARRISON SA, FRANCQUE S, et al. Elafibranor, an agonist of the peroxi-some proliferator-activated recep-tor-alpha and-delta, induces resolution of nonalcoholicsteatohepatitis without fibrosis worsening[J]. Gastroenterolo-gy, 2016, 150 (5) :1147-1159. e5.
    [27] JIANG XP, AI WB, WAN LY, et al. The roles of microRNAfamilies in hepatic fibrosis[J]. Cell Biosci, 2017, 7:34.
    [28] LI Z, JI L, SU S, et al. Leptin up-regulates microRNA-27a/b-3p level in hepatic stellate cells[J]. Exp Cell Res, 2018, 366 (1) :63-70.
    [29] HU D, HU Y, XU W, et al. miR-203 inhibits the expression ofcollagen-related genes and the proliferation of hepatic stellat-e cells through a SMAD3-dependent mechanism[J]. MolMed Rep, 2017, 16 (2) :1248-1254.
    [30] ZOU Y, CAI Y, LU D, et al. MicroRNA-146a-5p attenuatesliver fibrosis by suppressing profibrogenic effects of TGFβ1and lipopolysaccharide[J]. Cell Signal, 2017, 39:1-8.
    [31] CHEN J, YU Y, LI S. et al. MicroRNA-30a ameliorates he-patic fibrosis by inhibiting Beclin1-mediated autophagy[J].J Cell Mol Med, 2017, 21 (12) :3679-3692.
    [32] ZHENG J, DONG P, MAO Y, et al. lincRNA-p21 inhibits he-patic stellate cell activation and liver fibrogenesis via p21[J].FEBS J, 2015, 282 (24) :4810-4821.
    [33] ZHANG K, HAN X, ZHANG Z, et al. The liver-enriched lnc-LFAR1 promotes liver fibrosis by activating TGFβand Notchpathways[J]. Nat Commun, 2017, 8 (1) :144.
    [34] WANG R, DING Q, YAQOOB U, et al. Exosome adherenceand internalization by hepatic stellate cells triggers sphingosine1-phosphate-dependent migration[J]. J Biol Chem, 2015, 290 (52) :30684-30696.
    [35] CHARRIER A, CHEN R, CHEN L, et al. Exosomes mediate in-tercellular transfer of pro-fibro-genic connective tissuegrowth factor (CCN2) between hepatic stellate cells, the prin-cipal fibrotic cells in the liver[J]. Surgery, 2014, 156 (3) :548-555.
    [36] CHEN L, CHARRIER A, ZHOU Y, et al. Epigenetic regulationof connective tissue growth factor by MicroRNA-214 deliveryin exosomes from mouse or human hepatic stellate cells[J].Hepatology, 2014, 59 (3) :1118-1129.
    [37] CHEN L, BRIGSTOCK DR. Integrins and heparan sulfate pro-teoglycans on hepatic stellate cells (HSC) are novel receptorsfor HSC-derived exosomes[J]. FEBS Lett, 2016, 590 (23) :4263-4274.
    [38] DEVHARE PB, SASAKI R, SHRIVASTAVA S, et al. Exosome-mediated intercellular communica-tion between hepatitis Cvirus-infected hepatocytes and hepatic stellate cells[J]. JVirol, 2017, 91 (6) :1-14.
    [39] LEE YS, KIM SY, KO E, et al. Exosomes derived from palmit-ic acid-treated hepatocytes induce fibrotic activation of he-patic stellate cells[J]. Sci Rep, 2017, 7 (1) :3710.
    [40] SEO W, EUN HS, KIM SY, et al. Exosome-mediated activa-tion of toll-like receptor 3 in stellate cells stimulates interleukin-17 production by gammadelta T cells in liver fibrosis[J].Hepatology, 2016, 64 (2) :616-631.
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  • 收稿日期:  2018-08-30
  • 出版日期:  2019-03-20
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