The advances of profibrogenic research of leptin and its signaling pathways in hepatic fibrosis
-
摘要: 多种慢性肝病能导致肝纤维化,肝纤维化是发展为肝硬化的中间阶段。肝星状细胞的激活在肝纤维化的发生发展中起关键作用。在各种炎症刺激下,体内促肝纤维化因子激活其信号转导通路,使肝星状细胞的形态和功能发生变化,引起胶原沉积。瘦素作为一种促肝纤维化因子,通过其信号转导机制在肝纤维化发生发展中发挥重要作用。Abstract: Many kinds of chronic liver diseases can lead to hepatic fibrosis, which is the intermediate stage of liver cirrhosis.The activation of hepatic stellate cells plays a key role in the occurrence and development of liver fibrosis.Under the stimulation of inflammation, profibrogenic cytokines in the body activate their signaling pathways, so that the hepatic stellate cells change in morphology and function, causing collagen deposition.The leptin as a kind of profibrogenic cytokines, play an important role in the occurrence and development of hepatic fibrosis through its signal transduction mechanism.
-
Key words:
- liver cirrhosis /
- leptin /
- signal transduction
-
[1]Friedman SL.Hepatic stellate cells:protean, multifunctional, and enigmatic cells of the liver[J].Physiol Rev, 2008, 88 (1) :125-172. [1]Friedman SL.Hepatic stellate cells:protean, multifunctional, and enigmatic cells of the liver[J].Physiol Rev, 2008, 88 (1) :125-172. [2]Bertolani C, Marra F.The role of adipokines in liver fibrosis[J].Pathophysiology, 2008, 15 (2) :91-101. [2]Bertolani C, Marra F.The role of adipokines in liver fibrosis[J].Pathophysiology, 2008, 15 (2) :91-101. [3]Marra F, Bertolani C.Adipokines in liver diseases[J].Hepa-tology, 2009, 50 (3) :957-969. [3]Marra F, Bertolani C.Adipokines in liver diseases[J].Hepa-tology, 2009, 50 (3) :957-969. [4]Potter JJ, Womack L, Mezey E, et al.Transdifferentiationof rat hepatic stellate cells results in leptin expression[J].Biochem Biophys Res Commun, 1998, 244 (1) :178-182. [4]Potter JJ, Womack L, Mezey E, et al.Transdifferentiationof rat hepatic stellate cells results in leptin expression[J].Biochem Biophys Res Commun, 1998, 244 (1) :178-182. [5]Ikejima K, Honda H, Yoshikawa M, et al.Leptin augmentsinflammatory and profibrogenic responses in the murine liverinduced by hepatotoxic chemicals[J].Hepatology, 2001, 34 (2) :288-297. [5]Ikejima K, Honda H, Yoshikawa M, et al.Leptin augmentsinflammatory and profibrogenic responses in the murine liverinduced by hepatotoxic chemicals[J].Hepatology, 2001, 34 (2) :288-297. [6]Qamar A, Sheikh SZ, Masud A, et al.In vitro and in vivoprotection of stellate cells from apoptosis by leptin[J].DigDis Sci, 2006, 51 (10) :1697-1705. [6]Qamar A, Sheikh SZ, Masud A, et al.In vitro and in vivoprotection of stellate cells from apoptosis by leptin[J].DigDis Sci, 2006, 51 (10) :1697-1705. [7]Wang J, Leclercq I, Brymora JM, et al.Kupffer cells medi-ate leptin-induced liver fibrosis[J].Gastroenterology, 2009, 137 (2) :713-723. [7]Wang J, Leclercq I, Brymora JM, et al.Kupffer cells medi-ate leptin-induced liver fibrosis[J].Gastroenterology, 2009, 137 (2) :713-723. [8]Zhan SS, Jiang JX, Wu J, et al.Phagocytosis of apoptoticbodies by hepatic stellate cells induces NADPH oxidase andis associated with liver fibrosis in vivo[J].Hepatology, 2006, 43 (3) :435-443. [8]Zhan SS, Jiang JX, Wu J, et al.Phagocytosis of apoptoticbodies by hepatic stellate cells induces NADPH oxidase andis associated with liver fibrosis in vivo[J].Hepatology, 2006, 43 (3) :435-443. [9]Jiang JX, Mikami K, Shah VH, et al.Leptin induces phago-cytosis of apoptotic bodies by hepatic stellate cells via a Rhoguanosine triphosphatase-dependent mechanism[J].Hep-atology, 2008, 48 (5) :1497-1505. [9]Jiang JX, Mikami K, Shah VH, et al.Leptin induces phago-cytosis of apoptotic bodies by hepatic stellate cells via a Rhoguanosine triphosphatase-dependent mechanism[J].Hep-atology, 2008, 48 (5) :1497-1505. [10]Manolakopoulos S, Bethanis S, Liapi C, et al.An assessmentof serum leptin levels in patients with chronic viral hepatitis:aprospective study[J].BMC Gastroenterol, 2007, 7 (1) :17. [10]Manolakopoulos S, Bethanis S, Liapi C, et al.An assessmentof serum leptin levels in patients with chronic viral hepatitis:aprospective study[J].BMC Gastroenterol, 2007, 7 (1) :17. [11]Ahima RS, Osei SY.Leptin signaling[J].Physiol behavior, 2004, 81 (2) :223-241. [11]Ahima RS, Osei SY.Leptin signaling[J].Physiol behavior, 2004, 81 (2) :223-241. [12]Cao Q, Mak KM, Lieber CS.Leptin enhances alphal (I) col-lagen gene expression in LX-2 human hepatic stellate cellsthrough JAK-mediated H2O2-dependent MAPK pathways[J].J Cell Biochem, 2006, 97 (1) :188-197. [12]Cao Q, Mak KM, Lieber CS.Leptin enhances alphal (I) col-lagen gene expression in LX-2 human hepatic stellate cellsthrough JAK-mediated H2O2-dependent MAPK pathways[J].J Cell Biochem, 2006, 97 (1) :188-197. [13]Cao Q, Mak KM, Ren C, et al.Leptin stimulates tissue in-hibitor of metalloproteinase-1 in human hepatic stellatecells:respective roles of the JAK/STAT and JAK-mediatedH2O2-dependant MAPK pathways[J].J Biol Chem, 2004, 279 (6) :4292-4304. [13]Cao Q, Mak KM, Ren C, et al.Leptin stimulates tissue in-hibitor of metalloproteinase-1 in human hepatic stellatecells:respective roles of the JAK/STAT and JAK-mediatedH2O2-dependant MAPK pathways[J].J Biol Chem, 2004, 279 (6) :4292-4304. [14]Cao Q, Mak KM, Lieber CS.Leptin represses matrix metal-loproteinase-1 gene expression in LX2 human hepatic stel-late cells[J].J Hepatol, 2007, 46 (1) :124-133. [14]Cao Q, Mak KM, Lieber CS.Leptin represses matrix metal-loproteinase-1 gene expression in LX2 human hepatic stel-late cells[J].J Hepatol, 2007, 46 (1) :124-133. [15]Niu L, Wang X, Li J, et al.Leptin stimulates alphal (I) colla-gen expression in human hepatic stellate cells via the phos-phatidylinositol 3-kinase/Akt signalling pathway[J].LiverInt, 2007, 27 (9) :1265-1272. [15]Niu L, Wang X, Li J, et al.Leptin stimulates alphal (I) colla-gen expression in human hepatic stellate cells via the phos-phatidylinositol 3-kinase/Akt signalling pathway[J].LiverInt, 2007, 27 (9) :1265-1272. [16]Zhou Y, Jia X, Wang G, et al.PI-3 K/AKT and ERK signa-ling pathways mediate leptin-induced inhibition of PPARgamma gene expression in primary rat hepatic stellate cells[J].Mol Cell Biochem, 2009, 325 (1) :131-139. [16]Zhou Y, Jia X, Wang G, et al.PI-3 K/AKT and ERK signa-ling pathways mediate leptin-induced inhibition of PPARgamma gene expression in primary rat hepatic stellate cells[J].Mol Cell Biochem, 2009, 325 (1) :131-139. [17]Choi SS, Syn WK, Karaca GF, et al.Leptin promotes themyofibroblastic phenotype in hepatic stellate cells by activa-ting the hedgehog pathway[J].J Biol Chem, 2010, 285 (47) :36551-36560. [17]Choi SS, Syn WK, Karaca GF, et al.Leptin promotes themyofibroblastic phenotype in hepatic stellate cells by activa-ting the hedgehog pathway[J].J Biol Chem, 2010, 285 (47) :36551-36560. [18]De Minicis S, Seki E, Oesterreicher C, et al.Reduced nicotin-amide adenine dinucleotide phosphate oxidase mediates fibroticand inflammatory effects of leptin on hepatic stellate cells[J].Hepatology, 2008, 48 (6) :2016-2026. [18]De Minicis S, Seki E, Oesterreicher C, et al.Reduced nicotin-amide adenine dinucleotide phosphate oxidase mediates fibroticand inflammatory effects of leptin on hepatic stellate cells[J].Hepatology, 2008, 48 (6) :2016-2026. [19]Tang Y, Chen A.Curcumin prevents leptin raising glucoselevels in hepatic stellate cells by blocking translocation of glu-cose transporter-4 and increasing glucokinase[J].Br JPharmacol, 2010, 161 (5) :1137-1149. [19]Tang Y, Chen A.Curcumin prevents leptin raising glucoselevels in hepatic stellate cells by blocking translocation of glu-cose transporter-4 and increasing glucokinase[J].Br JPharmacol, 2010, 161 (5) :1137-1149. [20]Li J, Si HF, LüX, et al.Suppressive effects of leflunomideon leptin-induced TIMP-1 production involves on hepaticstellate cell proliferation and apoptosis[J].Eur J Pharmacol, 2008, 580 (1-2) :63-69. [20]Li J, Si HF, LüX, et al.Suppressive effects of leflunomideon leptin-induced TIMP-1 production involves on hepaticstellate cell proliferation and apoptosis[J].Eur J Pharmacol, 2008, 580 (1-2) :63-69. [21]Elinav E, Ali M, Bruck R, et al.Competitive inhibition of lep-tin signaling results in amelioration of liver fibrosis throughmodulation of stellate cell function[J].Hepatology, 2009, 49 (1) :278-286. [21]Elinav E, Ali M, Bruck R, et al.Competitive inhibition of lep-tin signaling results in amelioration of liver fibrosis throughmodulation of stellate cell function[J].Hepatology, 2009, 49 (1) :278-286. [22]Cao Q, Mak KM, Lieber CS.DLPC and SAMe combined pre-vent leptin-stimulated TIMP-1 production in LX-2 human he-patic stellate cells by inhibiting HO-mediated signal transduc-tion[J].Liver Int, 2006, 26 (2) :221-223. [22]Cao Q, Mak KM, Lieber CS.DLPC and SAMe combined pre-vent leptin-stimulated TIMP-1 production in LX-2 human he-patic stellate cells by inhibiting HO-mediated signal transduc-tion[J].Liver Int, 2006, 26 (2) :221-223. [23]Handy JA, Saxena NK, Fu P, et al.Adiponectin activation ofAMPK disrupts leptin-mediated hepatic fibrosis via suppres-sors of cytokine signaling (SOCS-3) [J].J Cell Biochem, 2010, 110 (5) :1195-1207. [23]Handy JA, Saxena NK, Fu P, et al.Adiponectin activation ofAMPK disrupts leptin-mediated hepatic fibrosis via suppres-sors of cytokine signaling (SOCS-3) [J].J Cell Biochem, 2010, 110 (5) :1195-1207. [24]Friedman SL.Evolving challenges in hepatic fibrosis[J].NatRev Gastroenterol Hepatol, 2010, 7 (8) :425-436. [24]Friedman SL.Evolving challenges in hepatic fibrosis[J].NatRev Gastroenterol Hepatol, 2010, 7 (8) :425-436.
本文二维码
计量
- 文章访问数: 3517
- HTML全文浏览量: 14
- PDF下载量: 740
- 被引次数: 0