Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells

Kong XY, Nesset CK, Damme M, Loeberg E-M, Lübke T, Maehlen J, Andersson KB, Roos N, Thoresen GH, Rustan AC, Kase ET, et al. (2014)
Disease Models & Mechanisms 7(3): 351-362.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
Kong, Xiang Yi; Nesset, Cecilie K.; Damme, MarkusUniBi; Loeberg, Else-Marit; Lübke, TorbenUniBi ; Maehlen, Jan; Andersson, Kristin B.; Roos, Norbert; Thoresen, G. Hege; Rustan, Arild C.; Kase, Eili T.; Eskild, Winnie
Abstract / Bemerkung
Human kidney predominant protein, NCU-G1, is a highly conserved protein with an unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no detectable expression of this gene were created using a gene-trap strategy, and Ncu-g1gt/gt mice were successfully characterized. Lysosomal disorders are mainly caused by lack of or malfunctioning of proteins in the endosomal-lysosomal pathway. The clinical symptoms vary, but often include liver dysfunction. Persistent liver damage activates fibrogenesis and, if unremedied, eventually leads to liver fibrosis/cirrhosis and death. We demonstrate that the disruption of Ncu-g1 results in spontaneous liver fibrosis in mice as the predominant phenotype. Evidence for an increased rate of hepatic cell death, oxidative stress and active fibrogenesis were detected in Ncu-g1gt/gt liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1gt/gt Kupffer cells. Because only a few transgenic mouse models have been identified with chronic liver injury and spontaneous liver fibrosis development, we propose that the Ncu-g1gt/gt mouse could be a valuable new tool in the development of novel treatments for the attenuation of fibrosis due to chronic liver damage.
NCU-G1; Fibrosis; Lysosome
Disease Models & Mechanisms
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Kong XY, Nesset CK, Damme M, et al. Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms. 2014;7(3):351-362.
Kong, X. Y., Nesset, C. K., Damme, M., Loeberg, E. - M., Lübke, T., Maehlen, J., Andersson, K. B., et al. (2014). Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms, 7(3), 351-362. doi:10.1242/dmm.014050
Kong, Xiang Yi, Nesset, Cecilie K., Damme, Markus, Loeberg, Else-Marit, Lübke, Torben, Maehlen, Jan, Andersson, Kristin B., et al. 2014. “Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells”. Disease Models & Mechanisms 7 (3): 351-362.
Kong, X. Y., Nesset, C. K., Damme, M., Loeberg, E. - M., Lübke, T., Maehlen, J., Andersson, K. B., Roos, N., Thoresen, G. H., Rustan, A. C., et al. (2014). Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms 7, 351-362.
Kong, X.Y., et al., 2014. Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms, 7(3), p 351-362.
X.Y. Kong, et al., “Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells”, Disease Models & Mechanisms, vol. 7, 2014, pp. 351-362.
Kong, X.Y., Nesset, C.K., Damme, M., Loeberg, E.-M., Lübke, T., Maehlen, J., Andersson, K.B., Roos, N., Thoresen, G.H., Rustan, A.C., Kase, E.T., Eskild, W.: Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells. Disease Models & Mechanisms. 7, 351-362 (2014).
Kong, Xiang Yi, Nesset, Cecilie K., Damme, Markus, Loeberg, Else-Marit, Lübke, Torben, Maehlen, Jan, Andersson, Kristin B., Roos, Norbert, Thoresen, G. Hege, Rustan, Arild C., Kase, Eili T., and Eskild, Winnie. “Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells”. Disease Models & Mechanisms 7.3 (2014): 351-362.
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HDAC inhibition improves autophagic and lysosomal function to prevent loss of subcutaneous fat in a mouse model of Cockayne syndrome.
Majora M, Sondenheimer K, Knechten M, Uthe I, Esser C, Schiavi A, Ventura N, Krutmann J., Sci Transl Med 10(456), 2018
PMID: 30158153
Increased glucose utilization and decreased fatty acid metabolism in myotubes from Glmp(gt/gt) mice.
Kong XY, Feng YZ, Eftestøl E, Kase ET, Haugum H, Eskild W, Rustan AC, Thoresen GH., Arch Physiol Biochem 122(1), 2016
PMID: 26707125
Age-dependent development of liver fibrosis in Glmp (gt/gt) mice.
Nesset CK, Kong XY, Damme M, Schjalm C, Roos N, Løberg EM, Eskild W., Fibrogenesis Tissue Repair 9(), 2016
PMID: 27141234
Lack of the Lysosomal Membrane Protein, GLMP, in Mice Results in Metabolic Dysregulation in Liver.
Kong XY, Kase ET, Herskedal A, Schjalm C, Damme M, Nesset CK, Thoresen GH, Rustan AC, Eskild W., PLoS One 10(6), 2015
PMID: 26047317

81 References

Daten bereitgestellt von Europe PubMed Central.

Lysosomal cell death at a glance.
Aits S, Jaattela M., J. Cell. Sci. 126(Pt 9), 2013
PMID: 23720375
Myeloperoxidase and elastase are only expressed by neutrophils in normal and in inflamed liver.
Amanzada A, Malik IA, Nischwitz M, Sultan S, Naz N, Ramadori G., Histochem. Cell Biol. 135(3), 2011
PMID: 21327394
Liver fibrosis.
Bataller R, Brenner DA., J. Clin. Invest. 115(2), 2005
PMID: 15690074
Distribution of lysosomal enzymes between parenchymal and Kupffer cells of rat liver.
Berg T, Boman D., Biochim. Biophys. Acta 321(2), 1973
PMID: 4357668
Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease.
Bernstein DL, Hulkova H, Bialer MG, Desnick RJ., J. Hepatol. 58(6), 2013
PMID: 23485521
Transcriptional profiling reveals novel markers of liver fibrogenesis: gremlin and insulin-like growth factor-binding proteins.
Boers W, Aarrass S, Linthorst C, Pinzani M, Elferink RO, Bosma P., J. Biol. Chem. 281(24), 2006
PMID: 16606614
Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression.
Canbay A, Feldstein AE, Higuchi H, Werneburg N, Grambihler A, Bronk SF, Gores GJ., Hepatology 38(5), 2003
PMID: 14578857
Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis.
Canbay A, Guicciardi ME, Higuchi H, Feldstein A, Bronk SF, Rydzewski R, Taniai M, Gores GJ., J. Clin. Invest. 112(2), 2003
PMID: 12865404
Proteolysis of insulin-like growth factors (IGF) and IGF binding proteins by cathepsin D.
Claussen M, Kubler B, Wendland M, Neifer K, Schmidt B, Zapf J, Braulke T., Endocrinology 138(9), 1997
PMID: 9275067
Hepcidin regulation of iron transport.
Collins JF, Wessling-Resnick M, Knutson MD., J. Nutr. 138(11), 2008
PMID: 18936232
Hepatic progenitors for liver disease: current position.
Conigliaro A, Brenner DA, Kisseleva T., Stem Cells Cloning 3(), 2010
PMID: 24198509
The cellular pathology of lysosomal diseases.
Cox TM, Cachon-Gonzalez MB., J. Pathol. 226(2), 2012
PMID: 21990005
Cholesteryl ester storage disease: pathologic changes in an affected fetus.
Desai PK, Astrin KH, Thung SN, Gordon RE, Short MP, Coates PM, Desnick RJ., Am. J. Med. Genet. 26(3), 1987
PMID: 3565483
Common antigens of mouse oval and biliary epithelial cells. Expression on newly formed hepatocytes.
Engelhardt NV, Factor VM, Yasova AK, Poltoranina VS, Baranov VN, Lasareva MN., Differentiation 45(1), 1990
PMID: 2292360
Common antigen of oval and biliary epithelial cells (A6) is a differentiation marker of epithelial and erythroid cell lineages in early development of the mouse.
Engelhardt NV, Factor VM, Medvinsky AL, Baranov VN, Lazareva MN, Poltoranina VS., Differentiation 55(1), 1993
PMID: 8299877
Intracellular trafficking during liver regeneration. Alterations in late endocytic and transcytotic pathways.
Fernandez MA, Turro S, Ingelmo-Torres M, Enrich C, Pol A., J. Hepatol. 40(1), 2004
PMID: 14672624
Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles.
Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Weiglein AH, Lammert F, Marschall HU, Tsybrovskyy O, Zatloukal K, Denk H, Trauner M., Gastroenterology 123(4), 2002
PMID: 12360485
Hepatic fibrosis -- overview.
Friedman SL., Toxicology 254(3), 2008
PMID: 18662740
The cell biology of lysosomal storage disorders.
Futerman AH, van Meer G., Nat. Rev. Mol. Cell Biol. 5(7), 2004
PMID: 15232573
Hepcidin and iron regulation, 10 years later.
Ganz T., Blood 117(17), 2011
PMID: 21346250
Fibrosis and cirrhosis reversibility - molecular mechanisms.
Gieling RG, Burt AD, Mann DA., Clin Liver Dis 12(4), 2008
PMID: 18984474
Liver iron transport.
Graham RM, Chua AC, Herbison CE, Olynyk JK, Trinder D., World J. Gastroenterol. 13(35), 2007
PMID: 17729394
Biomarkers of hepatic fibrosis, fibrogenesis and genetic pre-disposition pending between fiction and reality.
Gressner OA, Weiskirchen R, Gressner AM., J. Cell. Mol. Med. 11(5), 2007
PMID: 17979881
Cathepsin B contributes to TNF-alpha-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c.
Guicciardi ME, Deussing J, Miyoshi H, Bronk SF, Svingen PA, Peters C, Kaufmann SH, Gores GJ., J. Clin. Invest. 106(9), 2000
PMID: 11067865
Pathogenesis of liver fibrosis.
Hernandez-Gea V, Friedman SL., Annu Rev Pathol 6(), 2011
PMID: 21073339
LIver abnormalities in patients with Gaucher's disease.
James SP, Stromeyer FW, Chang C, Barranger JA., Gastroenterology 80(1), 1981
PMID: 7450398
Histopathologic approach to metabolic liver disease: Part 1.
Jevon GP, Dimmick JE., Pediatr. Dev. Pathol. 1(3), 1998
PMID: 10463278
The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress.
Kagedal K, Johansson U, Ollinger K., FASEB J. 15(9), 2001
PMID: 11427496
cDNA of a novel mRNA expressed predominantly in mouse kidney.
Kawamura T, Kuroda N, Kimura Y, Lazoura E, Okada N, Okada H., Biochem. Genet. 39(1-2), 2001
PMID: 11444019
Niemann-Pick disease type C: diagnosis and outcome in children, with particular reference to liver disease.
Kelly DA, Portmann B, Mowat AP, Sherlock S, Lake BD., J. Pediatr. 123(2), 1993
PMID: 7688422
Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice.
Kinoshita M, Uchida T, Sato A, Nakashima M, Nakashima H, Shono S, Habu Y, Miyazaki H, Hiroi S, Seki S., J. Hepatol. 53(5), 2010
PMID: 20739085
Autophagy, mitochondria and cell death in lysosomal storage diseases.
Kiselyov K, Jennigs JJ Jr, Rbaibi Y, Chu CT., Autophagy 3(3), 2007
PMID: 17329960
Mechanisms of fibrogenesis
Kisseleva T., Brenner D.., 2008
Anti-fibrogenic strategies and the regression of fibrosis.
Kisseleva T, Brenner DA., Best Pract Res Clin Gastroenterol 25(2), 2011
PMID: 21497747
A novel method for accurate collagen and biochemical assessment of pulmonary tissue utilizing one animal.
Kliment CR, Englert JM, Crum LP, Oury TD., Int J Clin Exp Pathol 4(4), 2011
PMID: 21577320
Liver inflammation and cytokine production, but not acute phase protein synthesis, accompany the adult liver progenitor (oval) cell response to chronic liver injury.
Knight B, Matthews VB, Akhurst B, Croager EJ, Klinken E, Abraham LJ, Olynyk JK, Yeoh G., Immunol. Cell Biol. 83(4), 2005
PMID: 16033531
Control of immune responses by savenger liver endothelial cells.
Knolle PA, Limmer A., Swiss Med Wkly 133(37-38), 2003
PMID: 14652798
Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages.
Knutson MD, Vafa MR, Haile DJ, Wessling-Resnick M., Blood 102(12), 2003
PMID: 12907459
Lysosomes and oxidative stress in aging and apoptosis.
Kurz T, Terman A, Gustafsson B, Brunk UT., Biochim. Biophys. Acta 1780(11), 2008
PMID: 18255041
Massive hepatic fibrosis in Gaucher's disease: clinico-pathological and radiological features.
Lachmann RH, Wight DG, Lomas DJ, Fisher NC, Schofield JP, Elias E, Cox TM., QJM 93(4), 2000
PMID: 10787452
Interactions between hepatic stellate cells and the immune system.
Maher JJ., Semin. Liver Dis. 21(3), 2001
PMID: 11586469
Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential.
Moles A, Tarrats N, Fernandez-Checa JC, Mari M., Hepatology 49(4), 2009
PMID: 19116891
Acidic sphingomyelinase controls hepatic stellate cell activation and in vivo liver fibrogenesis.
Moles A, Tarrats N, Morales A, Dominguez M, Bataller R, Caballeria J, Garcia-Ruiz C, Fernandez-Checa JC, Mari M., Am. J. Pathol. 177(3), 2010
PMID: 20651240
Cathepsin B overexpression due to acid sphingomyelinase ablation promotes liver fibrosis in Niemann-Pick disease.
Moles A, Tarrats N, Fernandez-Checa JC, Mari M., J. Biol. Chem. 287(2), 2011
PMID: 22102288
Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches.
Mormone E, George J, Nieto N., Chem. Biol. Interact. 193(3), 2011
PMID: 21803030
Erythrophagocytosis by liver macrophages (Kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis: implications for the pathogenesis of human nonalcoholic steatohepatitis.
Otogawa K, Kinoshita K, Fujii H, Sakabe M, Shiga R, Nakatani K, Ikeda K, Nakajima Y, Ikura Y, Ueda M, Arakawa T, Hato F, Kawada N., Am. J. Pathol. 170(3), 2007
PMID: 17322381
Lysosomal storage disease: revealing lysosomal function and physiology.
Parkinson-Lawrence EJ, Shandala T, Prodoehl M, Plew R, Borlace GN, Brooks DA., Physiology (Bethesda) 25(2), 2010
PMID: 20430954
Expression of matrix metalloproteinase-2 and -9 and of tissue inhibitor of matrix metalloproteinase-1 in liver regeneration from oval cells in rat.
Pham Van T, Couchie D, Martin-Garcia N, Laperche Y, Zafrani ES, Mavier P., Matrix Biol. 27(8), 2008
PMID: 18678246
Update on the pathophysiology of liver fibrosis.
Pinzani M, Macias-Barragan J., Expert Rev Gastroenterol Hepatol 4(4), 2010
PMID: 20678019
The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction.
Platt FM, Boland B, van der Spoel AC., J. Cell Biol. 199(5), 2012
PMID: 23185029
Liver fibrosis: a bidirectional model of fibrogenesis and resolution.
Ramachandran P, Iredale JP., QJM 105(9), 2012
PMID: 22647759
Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis.
Ramachandran P, Pellicoro A, Vernon MA, Boulter L, Aucott RL, Ali A, Hartland SN, Snowdon VK, Cappon A, Gordon-Walker TT, Williams MJ, Dunbar DR, Manning JR, van Rooijen N, Fallowfield JA, Forbes SJ, Iredale JP., Proc. Natl. Acad. Sci. U.S.A. 109(46), 2012
PMID: 23100531
New functions for an iron storage protein: the role of ferritin in immunity and autoimmunity.
Recalcati S, Invernizzi P, Arosio P, Cairo G., J. Autoimmun. 30(1-2), 2008
PMID: 18191543
Progenitor cells in diseased human liver.
Roskams TA, Libbrecht L, Desmet VJ., Semin. Liver Dis. 23(4), 2003
PMID: 14722815
Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion.
Ryckman C, Vandal K, Rouleau P, Talbot M, Tessier PA., J. Immunol. 170(6), 2003
PMID: 12626582
A gene network regulating lysosomal biogenesis and function.
Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, Di Malta C, Donaudy F, Embrione V, Polishchuk RS, Banfi S, Parenti G, Cattaneo E, Ballabio A., Science 325(5939), 2009
PMID: 19556463
NCU-G1 is a highly glycosylated integral membrane protein of the lysosome.
Schieweck O, Damme M, Schroder B, Hasilik A, Schmidt B, Lubke T., Biochem. J. 422(1), 2009
PMID: 19489740
Role for LAMP-2 in endosomal cholesterol transport.
Schneede A, Schmidt CK, Holtta-Vuori M, Heeren J, Willenborg M, Blanz J, Domanskyy M, Breiden B, Brodesser S, Landgrebe J, Sandhoff K, Ikonen E, Saftig P, Eskelinen EL., J. Cell. Mol. Med. 15(2), 2011
PMID: 19929948
Deficiency of the tetraspanin CD63 associated with kidney pathology but normal lysosomal function.
Schroder J, Lullmann-Rauch R, Himmerkus N, Pleines I, Nieswandt B, Orinska Z, Koch-Nolte F, Schroder B, Bleich M, Saftig P., Mol. Cell. Biol. 29(4), 2008
PMID: 19075008
The proteome of lysosomes.
Schroder BA, Wrocklage C, Hasilik A, Saftig P., Proteomics 10(22), 2010
PMID: 20957757
Animal models for the study of hepatic fibrosis.
Starkel P, Leclercq IA., Best Pract Res Clin Gastroenterol 25(2), 2011
PMID: 21497748
Human NCU-G1 can function as a transcription factor and as a nuclear receptor co-activator.
Steffensen KR, Bouzga M, Skjeldal F, Kasi C, Karahasan A, Matre V, Bakke O, Guerin S, Eskild W., BMC Mol. Biol. 8(), 2007
PMID: 18021396
Changes in lysosomal cathepsins during liver regeneration.
Suleiman SA, Jones GL, Singh H, Labrecque DR., Biochim. Biophys. Acta 627(1), 1980
PMID: 7353049
Heterogeneity of liver disorder in type B Niemann-Pick disease.
Takahashi T, Akiyama K, Tomihara M, Tokudome T, Nishinomiya F, Tazawa Y, Horinouchi K, Sakiyama T, Takada G., Hum. Pathol. 28(3), 1997
PMID: 9042807
Hepatocyte-specific disruption of Bcl-xL leads to continuous hepatocyte apoptosis and liver fibrotic responses.
Takehara T, Tatsumi T, Suzuki T, Rucker EB 3rd, Hennighausen L, Jinushi M, Miyagi T, Kanazawa Y, Hayashi N., Gastroenterology 127(4), 2004
PMID: 15480996
Lysosomal storage diseases: is impaired apoptosis a pathogenic mechanism?
Tardy C, Andrieu-Abadie N, Salvayre R, Levade T., Neurochem. Res. 29(5), 2004
PMID: 15139286
Terman A, Brunk UT., Int. J. Biochem. Cell Biol. 36(8), 2004
PMID: 15147719
Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes.
Vick B, Weber A, Urbanik T, Maass T, Teufel A, Krammer PH, Opferman JT, Schuchmann M, Galle PR, Schulze-Bergkamen H., Hepatology 49(2), 2009
PMID: 19127517
Lhx2-/- mice develop liver fibrosis.
Wandzioch E, Kolterud A, Jacobsson M, Friedman SL, Carlsson L., Proc. Natl. Acad. Sci. U.S.A. 101(47), 2004
PMID: 15536133
Chronic liver disease is triggered by taurine transporter knockout in the mouse.
Warskulat U, Borsch E, Reinehr R, Heller-Stilb B, Monnighoff I, Buchczyk D, Donner M, Flogel U, Kappert G, Soboll S, Beer S, Pfeffer K, Marschall HU, Gabrielsen M, Amiry-Moghaddam M, Ottersen OP, Dienes HP, Haussinger D., FASEB J. 20(3), 2006
PMID: 16421246
Hepatocyte-specific deletion of the antiapoptotic protein myeloid cell leukemia-1 triggers proliferation and hepatocarcinogenesis in mice.
Weber A, Boger R, Vick B, Urbanik T, Haybaeck J, Zoller S, Teufel A, Krammer PH, Opferman JT, Galle PR, Schuchmann M, Heikenwalder M, Schulze-Bergkamen H., Hepatology 51(4), 2010
PMID: 20099303
Mouse models of liver fibrosis.
Weiler-Normann C, Herkel J, Lohse AW., Z Gastroenterol 45(1), 2007
PMID: 17236120
HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis.
White C, Yuan X, Schmidt PJ, Bresciani E, Samuel TK, Campagna D, Hall C, Bishop K, Calicchio ML, Lapierre A, Ward DM, Liu P, Fleming MD, Hamza I., Cell Metab. 17(2), 2013
PMID: 23395172
Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo.
Zhan SS, Jiang JX, Wu J, Halsted C, Friedman SL, Zern MA, Torok NJ., Hepatology 43(3), 2006
PMID: 16496318

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