The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis

Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a...
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Autor*in:	Jordi Guiteras [verfasserIn] Élia Ripoll [verfasserIn] Núria Bolaños [verfasserIn] Laura De Ramon [verfasserIn] Pere Fontova [verfasserIn] Núria Lloberas [verfasserIn] Josep Maria Cruzado [verfasserIn] Josep Maria Aràn [verfasserIn] Anna Aviñó [verfasserIn] Ramon Eritja [verfasserIn] Montse Gomà [verfasserIn] Rosario Taco [verfasserIn] Josep Maria Grinyó [verfasserIn] Juan Torras [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	experimental lupus nephritis LN SLE siRNA IRF5 BLYSS

Übergeordnetes Werk:	In: Molecular Therapy: Nucleic Acids - Elsevier, 2013, 24(2021), Seite 807-821
Übergeordnetes Werk:	volume:24 ; year:2021 ; pages:807-821

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.omtn.2021.03.019

Katalog-ID:	DOAJ072384506

Internformat


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520			\|a Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease.
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700	0		\|a Pere Fontova \|e verfasserin \|4 aut
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700	0		\|a Montse Gomà \|e verfasserin \|4 aut
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700	0		\|a Josep Maria Grinyó \|e verfasserin \|4 aut
700	0		\|a Juan Torras \|e verfasserin \|4 aut
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Indexfelder

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publishDate	2021
allfields	10.1016/j.omtn.2021.03.019 doi (DE-627)DOAJ072384506 (DE-599)DOAJ74ac3e61a22d442ebac7639caa26d250 DE-627 ger DE-627 rakwb eng RM1-950 Jordi Guiteras verfasserin aut The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease. experimental lupus nephritis LN SLE siRNA IRF5 BLYSS Therapeutics. Pharmacology Élia Ripoll verfasserin aut Núria Bolaños verfasserin aut Laura De Ramon verfasserin aut Pere Fontova verfasserin aut Núria Lloberas verfasserin aut Josep Maria Cruzado verfasserin aut Josep Maria Aràn verfasserin aut Anna Aviñó verfasserin aut Ramon Eritja verfasserin aut Montse Gomà verfasserin aut Rosario Taco verfasserin aut Josep Maria Grinyó verfasserin aut Juan Torras verfasserin aut In Molecular Therapy: Nucleic Acids Elsevier, 2013 24(2021), Seite 807-821 (DE-627)718632702 (DE-600)2662631-7 21622531 nnns volume:24 year:2021 pages:807-821 https://doi.org/10.1016/j.omtn.2021.03.019 kostenfrei https://doaj.org/article/74ac3e61a22d442ebac7639caa26d250 kostenfrei http://www.sciencedirect.com/science/article/pii/S2162253121000901 kostenfrei https://doaj.org/toc/2162-2531 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2021 807-821
spelling	10.1016/j.omtn.2021.03.019 doi (DE-627)DOAJ072384506 (DE-599)DOAJ74ac3e61a22d442ebac7639caa26d250 DE-627 ger DE-627 rakwb eng RM1-950 Jordi Guiteras verfasserin aut The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease. experimental lupus nephritis LN SLE siRNA IRF5 BLYSS Therapeutics. Pharmacology Élia Ripoll verfasserin aut Núria Bolaños verfasserin aut Laura De Ramon verfasserin aut Pere Fontova verfasserin aut Núria Lloberas verfasserin aut Josep Maria Cruzado verfasserin aut Josep Maria Aràn verfasserin aut Anna Aviñó verfasserin aut Ramon Eritja verfasserin aut Montse Gomà verfasserin aut Rosario Taco verfasserin aut Josep Maria Grinyó verfasserin aut Juan Torras verfasserin aut In Molecular Therapy: Nucleic Acids Elsevier, 2013 24(2021), Seite 807-821 (DE-627)718632702 (DE-600)2662631-7 21622531 nnns volume:24 year:2021 pages:807-821 https://doi.org/10.1016/j.omtn.2021.03.019 kostenfrei https://doaj.org/article/74ac3e61a22d442ebac7639caa26d250 kostenfrei http://www.sciencedirect.com/science/article/pii/S2162253121000901 kostenfrei https://doaj.org/toc/2162-2531 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2021 807-821
allfields_unstemmed	10.1016/j.omtn.2021.03.019 doi (DE-627)DOAJ072384506 (DE-599)DOAJ74ac3e61a22d442ebac7639caa26d250 DE-627 ger DE-627 rakwb eng RM1-950 Jordi Guiteras verfasserin aut The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease. experimental lupus nephritis LN SLE siRNA IRF5 BLYSS Therapeutics. Pharmacology Élia Ripoll verfasserin aut Núria Bolaños verfasserin aut Laura De Ramon verfasserin aut Pere Fontova verfasserin aut Núria Lloberas verfasserin aut Josep Maria Cruzado verfasserin aut Josep Maria Aràn verfasserin aut Anna Aviñó verfasserin aut Ramon Eritja verfasserin aut Montse Gomà verfasserin aut Rosario Taco verfasserin aut Josep Maria Grinyó verfasserin aut Juan Torras verfasserin aut In Molecular Therapy: Nucleic Acids Elsevier, 2013 24(2021), Seite 807-821 (DE-627)718632702 (DE-600)2662631-7 21622531 nnns volume:24 year:2021 pages:807-821 https://doi.org/10.1016/j.omtn.2021.03.019 kostenfrei https://doaj.org/article/74ac3e61a22d442ebac7639caa26d250 kostenfrei http://www.sciencedirect.com/science/article/pii/S2162253121000901 kostenfrei https://doaj.org/toc/2162-2531 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2021 807-821
allfieldsGer	10.1016/j.omtn.2021.03.019 doi (DE-627)DOAJ072384506 (DE-599)DOAJ74ac3e61a22d442ebac7639caa26d250 DE-627 ger DE-627 rakwb eng RM1-950 Jordi Guiteras verfasserin aut The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease. experimental lupus nephritis LN SLE siRNA IRF5 BLYSS Therapeutics. Pharmacology Élia Ripoll verfasserin aut Núria Bolaños verfasserin aut Laura De Ramon verfasserin aut Pere Fontova verfasserin aut Núria Lloberas verfasserin aut Josep Maria Cruzado verfasserin aut Josep Maria Aràn verfasserin aut Anna Aviñó verfasserin aut Ramon Eritja verfasserin aut Montse Gomà verfasserin aut Rosario Taco verfasserin aut Josep Maria Grinyó verfasserin aut Juan Torras verfasserin aut In Molecular Therapy: Nucleic Acids Elsevier, 2013 24(2021), Seite 807-821 (DE-627)718632702 (DE-600)2662631-7 21622531 nnns volume:24 year:2021 pages:807-821 https://doi.org/10.1016/j.omtn.2021.03.019 kostenfrei https://doaj.org/article/74ac3e61a22d442ebac7639caa26d250 kostenfrei http://www.sciencedirect.com/science/article/pii/S2162253121000901 kostenfrei https://doaj.org/toc/2162-2531 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2021 807-821
allfieldsSound	10.1016/j.omtn.2021.03.019 doi (DE-627)DOAJ072384506 (DE-599)DOAJ74ac3e61a22d442ebac7639caa26d250 DE-627 ger DE-627 rakwb eng RM1-950 Jordi Guiteras verfasserin aut The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease. experimental lupus nephritis LN SLE siRNA IRF5 BLYSS Therapeutics. Pharmacology Élia Ripoll verfasserin aut Núria Bolaños verfasserin aut Laura De Ramon verfasserin aut Pere Fontova verfasserin aut Núria Lloberas verfasserin aut Josep Maria Cruzado verfasserin aut Josep Maria Aràn verfasserin aut Anna Aviñó verfasserin aut Ramon Eritja verfasserin aut Montse Gomà verfasserin aut Rosario Taco verfasserin aut Josep Maria Grinyó verfasserin aut Juan Torras verfasserin aut In Molecular Therapy: Nucleic Acids Elsevier, 2013 24(2021), Seite 807-821 (DE-627)718632702 (DE-600)2662631-7 21622531 nnns volume:24 year:2021 pages:807-821 https://doi.org/10.1016/j.omtn.2021.03.019 kostenfrei https://doaj.org/article/74ac3e61a22d442ebac7639caa26d250 kostenfrei http://www.sciencedirect.com/science/article/pii/S2162253121000901 kostenfrei https://doaj.org/toc/2162-2531 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2021 807-821
language	English
source	In Molecular Therapy: Nucleic Acids 24(2021), Seite 807-821 volume:24 year:2021 pages:807-821
sourceStr	In Molecular Therapy: Nucleic Acids 24(2021), Seite 807-821 volume:24 year:2021 pages:807-821
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	experimental lupus nephritis LN SLE siRNA IRF5 BLYSS Therapeutics. Pharmacology
isfreeaccess_bool	true
container_title	Molecular Therapy: Nucleic Acids
authorswithroles_txt_mv	Jordi Guiteras @@aut@@ Élia Ripoll @@aut@@ Núria Bolaños @@aut@@ Laura De Ramon @@aut@@ Pere Fontova @@aut@@ Núria Lloberas @@aut@@ Josep Maria Cruzado @@aut@@ Josep Maria Aràn @@aut@@ Anna Aviñó @@aut@@ Ramon Eritja @@aut@@ Montse Gomà @@aut@@ Rosario Taco @@aut@@ Josep Maria Grinyó @@aut@@ Juan Torras @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	718632702
id	DOAJ072384506
language_de	englisch
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callnumber-first	R - Medicine
author	Jordi Guiteras
spellingShingle	Jordi Guiteras misc RM1-950 misc experimental lupus nephritis misc LN misc SLE misc siRNA misc IRF5 misc BLYSS misc Therapeutics. Pharmacology The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis
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topic_title	RM1-950 The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis experimental lupus nephritis LN SLE siRNA IRF5 BLYSS
topic	misc RM1-950 misc experimental lupus nephritis misc LN misc SLE misc siRNA misc IRF5 misc BLYSS misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc experimental lupus nephritis misc LN misc SLE misc siRNA misc IRF5 misc BLYSS misc Therapeutics. Pharmacology
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title	The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis
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title_full	The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis
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author_browse	Jordi Guiteras Élia Ripoll Núria Bolaños Laura De Ramon Pere Fontova Núria Lloberas Josep Maria Cruzado Josep Maria Aràn Anna Aviñó Ramon Eritja Montse Gomà Rosario Taco Josep Maria Grinyó Juan Torras
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title_sort	gene silencing of irf5 and blyss effectively modulates the outcome of experimental lupus nephritis
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title_auth	The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis
abstract	Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease.
abstractGer	Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease.
abstract_unstemmed	Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease.
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title_short	The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis
url	https://doi.org/10.1016/j.omtn.2021.03.019 https://doaj.org/article/74ac3e61a22d442ebac7639caa26d250 http://www.sciencedirect.com/science/article/pii/S2162253121000901 https://doaj.org/toc/2162-2531
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The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis

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