RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease
Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an expe...
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| Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2024-08, Vol.265, p.110279, Article 110279 |
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| creator | Tatomir, Alexandru Vlaicu, Sonia Nguyen, Vinh Luzina, Irina G. Atamas, Sergei P. Drachenberg, Cinthia Papadimitriou, John Badea, Tudor C. Rus, Horea G. Rus, Violeta |
| description | Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17+ and IFNγ+ cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. Thus, RGC-32 is a unique mediator shared by the Th17 and Th1 dependent proinflammatory and profibrotic pathways and a potential novel therapeutic target in the treatment of immune complex mediated glomerulonephritis such as lupus nephritis. |
| doi_str_mv | 10.1016/j.clim.2024.110279 |
| format | Article |
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We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17+ and IFNγ+ cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. Thus, RGC-32 is a unique mediator shared by the Th17 and Th1 dependent proinflammatory and profibrotic pathways and a potential novel therapeutic target in the treatment of immune complex mediated glomerulonephritis such as lupus nephritis.</description><identifier>ISSN: 1521-6616</identifier><identifier>ISSN: 1521-7035</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1016/j.clim.2024.110279</identifier><identifier>PMID: 38878807</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Autoimmunity ; Disease Models, Animal ; Fibrosis ; Humans ; Inflammation - immunology ; Kidney - immunology ; Kidney - pathology ; Lupus Nephritis - immunology ; Lupus Nephritis - pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nephrotoxic nephritis ; Nuclear Proteins ; Response gene to complement-32 ; Th1 Cells - immunology ; Th17 Cells - immunology</subject><ispartof>Clinical immunology (Orlando, Fla.), 2024-08, Vol.265, p.110279, Article 110279</ispartof><rights>2023</rights><rights>Copyright © 2023. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c237t-e2761e8e82caa2f52fb53ea7a22d0bbbd693fe1582c6b47d3e11299ce5a16aee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clim.2024.110279$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,46004</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38878807$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tatomir, Alexandru</creatorcontrib><creatorcontrib>Vlaicu, Sonia</creatorcontrib><creatorcontrib>Nguyen, Vinh</creatorcontrib><creatorcontrib>Luzina, Irina G.</creatorcontrib><creatorcontrib>Atamas, Sergei P.</creatorcontrib><creatorcontrib>Drachenberg, Cinthia</creatorcontrib><creatorcontrib>Papadimitriou, John</creatorcontrib><creatorcontrib>Badea, Tudor C.</creatorcontrib><creatorcontrib>Rus, Horea G.</creatorcontrib><creatorcontrib>Rus, Violeta</creatorcontrib><title>RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17+ and IFNγ+ cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. Thus, RGC-32 is a unique mediator shared by the Th17 and Th1 dependent proinflammatory and profibrotic pathways and a potential novel therapeutic target in the treatment of immune complex mediated glomerulonephritis such as lupus nephritis.</description><subject>Animals</subject><subject>Autoimmunity</subject><subject>Disease Models, Animal</subject><subject>Fibrosis</subject><subject>Humans</subject><subject>Inflammation - immunology</subject><subject>Kidney - immunology</subject><subject>Kidney - pathology</subject><subject>Lupus Nephritis - immunology</subject><subject>Lupus Nephritis - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Nephrotoxic nephritis</subject><subject>Nuclear Proteins</subject><subject>Response gene to complement-32</subject><subject>Th1 Cells - immunology</subject><subject>Th17 Cells - immunology</subject><issn>1521-6616</issn><issn>1521-7035</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMorq7-AQ_So5fWfGyTFrzIoquwIIhevIQ0mWLWfqxJq_Tfm9Lq0dMMM-_7MvMgdEFwQjDh17tEV7ZOKKarhBBMRX6ATkhKSSwwSw_nnnPCF-jU-x3GOKWUH6MFyzKRZVicoLfnzTpmNKrBWNWBj_autU1ZqbpWXeuGSDVmnJW2cG1ndbRX3fu3Gnxkm8jWdd9APHtN9GFNA0NkrAfl4QwdlarycD7XJXq9v3tZP8Tbp83j-nYba8pEFwMVnEAGGdVK0TKlZZEyUEJRanBRFIbnrASShj0vVsIwIITmuYZUEa4A2BJdTbnhzM8efCdr6zVUlWqg7b1kmGciJXlOgpROUu1a7x2Ucu9srdwgCZYjU7mTI1M5MpUT02C6nPP7Irz6Z_mFGAQ3kwDCl18WnPTaQqMDFge6k6a1_-X_AFr5iRo</recordid><startdate>202408</startdate><enddate>202408</enddate><creator>Tatomir, Alexandru</creator><creator>Vlaicu, Sonia</creator><creator>Nguyen, Vinh</creator><creator>Luzina, Irina G.</creator><creator>Atamas, Sergei P.</creator><creator>Drachenberg, Cinthia</creator><creator>Papadimitriou, John</creator><creator>Badea, Tudor C.</creator><creator>Rus, Horea G.</creator><creator>Rus, Violeta</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202408</creationdate><title>RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease</title><author>Tatomir, Alexandru ; Vlaicu, Sonia ; Nguyen, Vinh ; Luzina, Irina G. ; Atamas, Sergei P. ; Drachenberg, Cinthia ; Papadimitriou, John ; Badea, Tudor C. ; Rus, Horea G. ; Rus, Violeta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c237t-e2761e8e82caa2f52fb53ea7a22d0bbbd693fe1582c6b47d3e11299ce5a16aee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Autoimmunity</topic><topic>Disease Models, Animal</topic><topic>Fibrosis</topic><topic>Humans</topic><topic>Inflammation - immunology</topic><topic>Kidney - immunology</topic><topic>Kidney - pathology</topic><topic>Lupus Nephritis - immunology</topic><topic>Lupus Nephritis - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Nephrotoxic nephritis</topic><topic>Nuclear Proteins</topic><topic>Response gene to complement-32</topic><topic>Th1 Cells - immunology</topic><topic>Th17 Cells - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tatomir, Alexandru</creatorcontrib><creatorcontrib>Vlaicu, Sonia</creatorcontrib><creatorcontrib>Nguyen, Vinh</creatorcontrib><creatorcontrib>Luzina, Irina G.</creatorcontrib><creatorcontrib>Atamas, Sergei P.</creatorcontrib><creatorcontrib>Drachenberg, Cinthia</creatorcontrib><creatorcontrib>Papadimitriou, John</creatorcontrib><creatorcontrib>Badea, Tudor C.</creatorcontrib><creatorcontrib>Rus, Horea G.</creatorcontrib><creatorcontrib>Rus, Violeta</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical immunology (Orlando, Fla.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tatomir, Alexandru</au><au>Vlaicu, Sonia</au><au>Nguyen, Vinh</au><au>Luzina, Irina G.</au><au>Atamas, Sergei P.</au><au>Drachenberg, Cinthia</au><au>Papadimitriou, John</au><au>Badea, Tudor C.</au><au>Rus, Horea G.</au><au>Rus, Violeta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease</atitle><jtitle>Clinical immunology (Orlando, Fla.)</jtitle><addtitle>Clin Immunol</addtitle><date>2024-08</date><risdate>2024</risdate><volume>265</volume><spage>110279</spage><pages>110279-</pages><artnum>110279</artnum><issn>1521-6616</issn><issn>1521-7035</issn><eissn>1521-7035</eissn><abstract>Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17+ and IFNγ+ cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. 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| subjects | Animals Autoimmunity Disease Models, Animal Fibrosis Humans Inflammation - immunology Kidney - immunology Kidney - pathology Lupus Nephritis - immunology Lupus Nephritis - pathology Mice Mice, Inbred C57BL Mice, Knockout Nephrotoxic nephritis Nuclear Proteins Response gene to complement-32 Th1 Cells - immunology Th17 Cells - immunology |
| title | RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease |
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