Role of adiponectin in liver fibrogenesis:progress in basic and clinical research
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摘要: 脂联素(ADN)具有多种生物学作用。近年研究表明其可抑制肝纤维化的发展。一些动物实验显示ADN基因敲除(ADN-KO)鼠易发生纤维化,可能与ADN具有抗氧化应激及抗炎作用有关。肝星状细胞(HSC)在肝纤维化中起核心作用,ADN可抑制HSC增殖、迁移,促进其凋亡。临床研究报道ADN与慢性肝病的纤维化进展有关,为肝纤维化的无创性诊断提供新的方向。进一步分析ADN的抗肝纤维化机制有重要意义。Abstract: Adiponectin possesses many biological effects.Recent studies have found that adiponectin can inhibit the development of hepatic fibrosis.Some animal experiments demonstrate that adiponectin-knockout (ADN-KO) mice tend to develop severe hepatic fibrosis which may be associated with anti-oxidative stress and anti-inflammatory effects of adiponectin.Hepatic stellate cell (HSC) play a central role in liver fibrogenesis.Studies showed that adiponectin can inhibit proliferation, migration of HSC and promote its apoptosis.Clinical researches also reported that adiponectin was related to progression of hepatic fibrosis in chronic liver diseases, which is a new way for the non-invasive diagnosis of hepatic fibrosis.It is necessary to investigate the precise mechanism of adiponectin on hepatic fibrosis.
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Key words:
- adiponectin /
- liver cirrhosis
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[1]Hug C, Wang J, Ahmad NS, et al.T-cadherin is a receptorfor hexameric and high-molecularweight forms ofAcrp30/adiponectin[J].Proc Natl Acad Sci U S A, 2004, 101 (28) :10308-10313. [2]Kamada Y, Tamura S, Matsumoto H, et al.Enhancedcarbon tetrachloride-induced liver fibrosis in mice lackingadiponectin[J].Gastroenterology, 2003, 125 (6) :1796-1807. [3]Handy JA, Saxena NK, Fu P, et al.Adiponectin activationof AMPK disrupts leptin-mediated hepatic fibrosis viasuppressors of cytokine signaling (SOCS-3) [J].J CellBiochem, 2010, 110 (5) :1195-1207. [4]Asano T, Omata M, Kadowaki T, et al.Adiponectin knockoutmice on high fat diet develop fibrosing steatohepatitis[J].JGastroenterol Hepatol, 2009, 24 (10) :1669-1676. [5]Kamada Y, Matsumoto H, Tamura S, et al.Hypoadip-onectinemia accelerates hepatic tumor formation in anonalcoholic steatohepatitis mouse model[J].J Hepatol, 2007, 47 (4) :556-564. [6]Fukushima J, Kamada Y, Yoshida Y, et al.Adiponectinprevents progression of steatohepatitis in mice byregulating oxidative stress and Kupffer cell phenotypepolarizationhep[J].Hepatol Res, 2009, 39 (7) :724-738. [7]Tomita K, Oike Y, Teratani T, et al.Hepatic AdipoR2 signalingplays a protective role against progression of nonalcoholicsteatohepatitis in mice[J].Hepatology, 2008, 48 (2) :458-473. [8]You M, Rogers CQ.Adiponectin:a key adipokine in alcoholicfatty liver[J].Exp Biol Med, 2009, 234 (8) :850-859. [9]Ding X, Saxena NK, Lin S, et al.The roles of leptin andadiponectin:a novel paradigm in adipocytokine regulation ofliver fibrosis and stellate cell biology[J].Am J Pathol, 2005, 166 (6) :1655-1669. [10]Da Silva Morais A, Abarca-Quinones J, Guigas B, et al.Development of hepatic fibrosis occurs normally in AMPK-deficient mice[J].Clin Sci, 2009, 118 (6) :411-420. [11]Zhang J, Tan L, Lin J, et al.Adenovirus-mediatedoverexpression of AMP-activated protein kinase inducesLX2 cell apoptosis[J].Nan Fang Yi Ke Da Xue Xue Bao, 2007, 27 (6) :821-823. [12]Adach M, Brenneri DA.High molecular weight adip-onectininhibits proliferation of hepatic stellate cells via activationof adenosine monophosphate-activated protein kinase[J].Hepatology, 2008, 47 (2) :677-685. [13]Urtasun R, Nieto N.Hepatic stellate cells and oxidativestress[J].Rev Esp Enferm Dig, 2007, 99 (4) :223-230. [14]Aram G, Potter JJ, Liu X, et al.Lack of inducible nitricoxide synthase leads to increased hepatic apoptosis anddecreased fibrosis in mice after chronic carbon tetrachlorideadministration[J].Hepatology, 2008, 47 (6) :2051-2058. [15]Liu YD, Ramezani-Moghadam M, George J, et al.Ku-pfferCells and s inusoidal endothelial cells mediate the anti-fibrogenic effects of adiponectin on hepatic stellate cells[R].Hepatol Int, 2010, 4 (1) :2-93. [16]Musso G, Gambino R, Biroli G, et al.Hypoadiponec-tinemiapredicts the severity of hepatic fibrosis and pancreaticbeta-cell dysfunction in nondiabetic nonobese patients withnonalcoholic steatohepatitis[J].Am J Gastroenterol, 2005, 100 (11) :2438-2446. [17]Kaser S, Moschen A, Cayon A, et al.Adiponectin and itsreceptors in nonalcoholic steatohepatitis[J].Gut, 2005, 54 (1) :117-121. [18]Nazal L, Riquelme A, Soíls N, et al.Hypoadipone-ctinemiaand its association with liver fibrosis in morbidly obese patients[J].Obes Surg, 2010, 20 (10) :1400-1407. [19]Wedemeyer I, Bechmann LP, Odenthal M, et al.Adip-onectininhibits steatotic CD95/Fas up-regulation by hepatocytes:Therapeutic implications for hepatitis C[J].J Hepatol, 2009, 50 (1) :140-149. [20]Jonsson JR, Moschen AR, Hickman LJ, et al.Adiponectinand its receptors in patients with chronic hepatitis C[J].JHepatol, 2005, 43 (6) :929-936. [21]Latif HA, Assal HS, Mahmoud M, et al.Role of serumadiponectin level in the development of liver cirrhosis inpatients with hepatitis C virus[J].Clin Exp Med, 2010, Aug17.[Epub ahead of print] [22]Hui CK, Zhang HY, Lee NP, et al.Serum adiponectin isincreased in advancing liver fibrosis and declines with reduction in fibrosis in chronic hepatitis B[J].J Hepatol, 2007, 47 (2) :191-202. [23]Liu CJ, Chen PJ, Lai MY, et al.High serum adiponectincorrelates with advanced liver disease in patients with chronichepatitis B virus infection[J].Hepatol Int, 2009, 3 (2) :364-370. [24]Tacke F, Horn R, Luedde T, et al.High adiponectin in chronic liverdisease and cholestasis suggests biliary route of adiponectinexcretion in vivo[J].J Hepatol, 2005, 42 (5) :666-673. [25]Wong VW, Wong GL, Yu J, et al.Interaction of adipokinesand hepatitis B virus on histological liver injury in theChinese[J].Am J Gastroenterol, 2010, 105 (1) :132-138.
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