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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans

Liu, Kui (author)
Li, Quan-Zhen (author)
Delgado-Vega, Angelica M. (author)
Uppsala universitet,Institutionen för genetik och patologi
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Abelson, Anna-Karin (author)
Uppsala universitet,Institutionen för genetik och patologi
Sánchez, Elena (author)
Kelly, Jennifer A. (author)
Li, Li (author)
Liu, Yang (author)
Zhou, Jinchun (author)
Yan, Mei (author)
Ye, Qiu (author)
Liu, Shenxi (author)
Xie, Chun (author)
Zhou, Xin J. (author)
Chung, Sharon A. (author)
Pons-Estel, Bernardo (author)
Witte, Torsten (author)
de Ramón, Enrique (author)
Bae, Sang-Cheol (author)
Barizzone, Nadia (author)
Sebastiani, Gian Domenico (author)
Merrill, Joan T. (author)
Gregersen, Peter K. (author)
Gilkeson, Gary G. (author)
Kimberly, Robert P. (author)
Vyse, Timothy J. (author)
Kim, Il (author)
D'Alfonso, Sandra (author)
Martin, Javier (author)
Harley, John B. (author)
Criswell, Lindsey A. (author)
Wakeland, Edward K. (author)
Alarcón-Riquelme, Marta E. (author)
Uppsala universitet,Institutionen för genetik och patologi
Mohan, Chandra (author)
Danieli, M.G. (author)
Galeazzi, M. (author)
Querini, P.R. (author)
Migliaresi, S. (author)
Scherbarth, H.R. (author)
Lopez, J.A. (author)
Motta, E.L. (author)
Gamron, S. (author)
Drenkard, C. (author)
Menso, E. (author)
Allievi, A. (author)
Tate, G.A. (author)
Presas, J.L. (author)
Palatnik, S.A. (author)
Abdala, M. (author)
Bearzotti, M. (author)
Alvarellos, A. (author)
Caeiro, F. (author)
Bertoli, A. (author)
Paira, S. (author)
Roverano, S. (author)
Graf, C.E. (author)
Bertero, E. (author)
Caprarulo, C. (author)
Buchanan, G. (author)
Guillerón, C. (author)
Grimaudo, S. (author)
Manni, J. (author)
Catoggio, L.J. (author)
Soriano, E.R. (author)
Santos, C.D. (author)
Prigione, C. (author)
Ramos, F.A. (author)
Navarro, S.M. (author)
Berbotto, G.A. (author)
Jorfen, M. (author)
Romero, E.J. (author)
Garcia, M.A. (author)
Marcos, J.C. (author)
Marcos, A.I. (author)
Perandones, C.E. (author)
Eimon, A. (author)
Battagliotti, C.G. (author)
Armadi-Simab, K. (author)
Gross, W.L. (author)
Gromica-Ihle, E. (author)
Peter, H.H. (author)
Manger, K. (author)
Schnarr, S. (author)
Zeidler, H. (author)
Schmidt, R.E. (author)
Ortego, N. (author)
Callejas, J.L. (author)
Jiménez-Alonso, J. (author)
Sabio, M. (author)
Sánchez-Román, J. (author)
Garcia-Hernandez, F.J. (author)
Camps, M. (author)
López-Nevot, M.A. (author)
González-Escribano, M.F. (author)
Harley, J.H. (author)
Riquelme, M.A. (author)
Kimberly, R. (author)
Criswell, L. (author)
Langefeld, C. (author)
Tsao, B. (author)
Jacob, C. (author)
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 (creator_code:org_t)
2009
2009
English.
In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.

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MEDICIN

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By the author/editor
Liu, Kui
Li, Quan-Zhen
Delgado-Vega, An ...
Abelson, Anna-Ka ...
Sánchez, Elena
Kelly, Jennifer ...
show more...
Li, Li
Liu, Yang
Zhou, Jinchun
Yan, Mei
Ye, Qiu
Liu, Shenxi
Xie, Chun
Zhou, Xin J.
Chung, Sharon A.
Pons-Estel, Bern ...
Witte, Torsten
de Ramón, Enriqu ...
Bae, Sang-Cheol
Barizzone, Nadia
Sebastiani, Gian ...
Merrill, Joan T.
Gregersen, Peter ...
Gilkeson, Gary G ...
Kimberly, Robert ...
Vyse, Timothy J.
Kim, Il
D'Alfonso, Sandr ...
Martin, Javier
Harley, John B.
Criswell, Lindse ...
Wakeland, Edward ...
Alarcón-Riquelme ...
Mohan, Chandra
Danieli, M.G.
Galeazzi, M.
Querini, P.R.
Migliaresi, S.
Scherbarth, H.R.
Lopez, J.A.
Motta, E.L.
Gamron, S.
Drenkard, C.
Menso, E.
Allievi, A.
Tate, G.A.
Presas, J.L.
Palatnik, S.A.
Abdala, M.
Bearzotti, M.
Alvarellos, A.
Caeiro, F.
Bertoli, A.
Paira, S.
Roverano, S.
Graf, C.E.
Bertero, E.
Caprarulo, C.
Buchanan, G.
Guillerón, C.
Grimaudo, S.
Manni, J.
Catoggio, L.J.
Soriano, E.R.
Santos, C.D.
Prigione, C.
Ramos, F.A.
Navarro, S.M.
Berbotto, G.A.
Jorfen, M.
Romero, E.J.
Garcia, M.A.
Marcos, J.C.
Marcos, A.I.
Perandones, C.E.
Eimon, A.
Battagliotti, C. ...
Armadi-Simab, K.
Gross, W.L.
Gromica-Ihle, E.
Peter, H.H.
Manger, K.
Schnarr, S.
Zeidler, H.
Schmidt, R.E.
Ortego, N.
Callejas, J.L.
Jiménez-Alonso, ...
Sabio, M.
Sánchez-Román, J ...
Garcia-Hernandez ...
Camps, M.
López-Nevot, M.A ...
González-Escriba ...
Harley, J.H.
Riquelme, M.A.
Kimberly, R.
Criswell, L.
Langefeld, C.
Tsao, B.
Jacob, C.
show less...
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Journal of Clini ...
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