Absence of the Lectin Activation Pathway of Complement Ameliorates Proteinuria-Induced Renal Injury
Proteinuria is an adverse prognostic feature in renal diseases. In proteinuric nephropathies, filtered proteins exert an injurious effect on the renal tubulointerstitium, resulting in inflammation and fibrosis. In the present study, we assessed to what extent complement activation via the lectin pat...
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02238/full |
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| author | Samy Alghadban Samy Alghadban Hany I. Kenawy Hany I. Kenawy Thomas Dudler Wilhelm J. Schwaeble Wilhelm J. Schwaeble Nigel J. Brunskill Nigel J. Brunskill |
| author_facet | Samy Alghadban Samy Alghadban Hany I. Kenawy Hany I. Kenawy Thomas Dudler Wilhelm J. Schwaeble Wilhelm J. Schwaeble Nigel J. Brunskill Nigel J. Brunskill |
| author_sort | Samy Alghadban |
| collection | DOAJ |
| description | Proteinuria is an adverse prognostic feature in renal diseases. In proteinuric nephropathies, filtered proteins exert an injurious effect on the renal tubulointerstitium, resulting in inflammation and fibrosis. In the present study, we assessed to what extent complement activation via the lectin pathway may contribute to renal injury in response to proteinuria-related stress in proximal tubular cells. We used the well-established mouse model of protein overload proteinuria (POP) to assess the effect of lectin pathway inhibition on renal injury and fibrotic changes characteristic of proteinuric nephropathy. To this end, we compared experimental outcomes in wild type mice with MASP-2-deficient mice or wild type mice treated with MASP-2 inhibitor to block lectin pathway functional activity. Multiple markers of renal injury were assessed including renal function, proteinuria, macrophage infiltration, and cytokine release profiles. Both MASP-2-deficient and MASP-2 inhibitor-treated wild type mice exhibited renoprotection from proteinuria with significantly less tubulointerstitial injury when compared to isotype control antibody treated mice. This indicates that therapeutic targeting of MASP-2 in proteinuric nephropathies may offer a useful strategy in the clinical management of proteinuria associated pathologies in a variety of different underlying renal diseases. |
| first_indexed | 2024-12-11T22:22:01Z |
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| id | doaj.art-0988e2c2c5184092adff49d40b5b157b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T22:22:01Z |
| publishDate | 2019-09-01 |
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| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0988e2c2c5184092adff49d40b5b157b2022-12-22T00:48:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-09-011010.3389/fimmu.2019.02238465583Absence of the Lectin Activation Pathway of Complement Ameliorates Proteinuria-Induced Renal InjurySamy Alghadban0Samy Alghadban1Hany I. Kenawy2Hany I. Kenawy3Thomas Dudler4Wilhelm J. Schwaeble5Wilhelm J. Schwaeble6Nigel J. Brunskill7Nigel J. Brunskill8Department of Infection, Immunity and Inflammation, College of Life Sciences, University of Leicester, Leicester, United KingdomZoology Department, Faculty of Science, Al-Azhar University, Cairo, EgyptDepartment of Infection, Immunity and Inflammation, College of Life Sciences, University of Leicester, Leicester, United KingdomMicrobiology and Immunology Department, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptOmeros Corporation, Seattle, WA, United StatesDepartment of Infection, Immunity and Inflammation, College of Life Sciences, University of Leicester, Leicester, United KingdomDepartment of Veterinary Medicine, University of Cambridge, Cambridge, United KingdomDepartment of Infection, Immunity and Inflammation, College of Life Sciences, University of Leicester, Leicester, United KingdomDepartment of Nephrology, Leicester General Hospital, Leicester, United KingdomProteinuria is an adverse prognostic feature in renal diseases. In proteinuric nephropathies, filtered proteins exert an injurious effect on the renal tubulointerstitium, resulting in inflammation and fibrosis. In the present study, we assessed to what extent complement activation via the lectin pathway may contribute to renal injury in response to proteinuria-related stress in proximal tubular cells. We used the well-established mouse model of protein overload proteinuria (POP) to assess the effect of lectin pathway inhibition on renal injury and fibrotic changes characteristic of proteinuric nephropathy. To this end, we compared experimental outcomes in wild type mice with MASP-2-deficient mice or wild type mice treated with MASP-2 inhibitor to block lectin pathway functional activity. Multiple markers of renal injury were assessed including renal function, proteinuria, macrophage infiltration, and cytokine release profiles. Both MASP-2-deficient and MASP-2 inhibitor-treated wild type mice exhibited renoprotection from proteinuria with significantly less tubulointerstitial injury when compared to isotype control antibody treated mice. This indicates that therapeutic targeting of MASP-2 in proteinuric nephropathies may offer a useful strategy in the clinical management of proteinuria associated pathologies in a variety of different underlying renal diseases.https://www.frontiersin.org/article/10.3389/fimmu.2019.02238/fulllectin pathwayproteinuriakidneyMASPMBL-associated serine proteasesnephropathy |
| spellingShingle | Samy Alghadban Samy Alghadban Hany I. Kenawy Hany I. Kenawy Thomas Dudler Wilhelm J. Schwaeble Wilhelm J. Schwaeble Nigel J. Brunskill Nigel J. Brunskill Absence of the Lectin Activation Pathway of Complement Ameliorates Proteinuria-Induced Renal Injury Frontiers in Immunology lectin pathway proteinuria kidney MASP MBL-associated serine proteases nephropathy |
| title | Absence of the Lectin Activation Pathway of Complement Ameliorates Proteinuria-Induced Renal Injury |
| title_full | Absence of the Lectin Activation Pathway of Complement Ameliorates Proteinuria-Induced Renal Injury |
| title_fullStr | Absence of the Lectin Activation Pathway of Complement Ameliorates Proteinuria-Induced Renal Injury |
| title_full_unstemmed | Absence of the Lectin Activation Pathway of Complement Ameliorates Proteinuria-Induced Renal Injury |
| title_short | Absence of the Lectin Activation Pathway of Complement Ameliorates Proteinuria-Induced Renal Injury |
| title_sort | absence of the lectin activation pathway of complement ameliorates proteinuria induced renal injury |
| topic | lectin pathway proteinuria kidney MASP MBL-associated serine proteases nephropathy |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02238/full |
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