ADAMTS7-Mediated Complement Factor H Degradation Potentiates Complement Activation to Contributing to Renal Injuries.
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
01 02 2023
01 02 2023
Historique:
received:
27
05
2022
accepted:
31
10
2022
pmc-release:
01
02
2024
entrez:
3
2
2023
pubmed:
4
2
2023
medline:
8
2
2023
Statut:
ppublish
Résumé
The dysfunction of complement factor H (CFH), the main soluble complement negative regulator, potentiates various complement-induced renal injuries. However, insights into the underlying mechanism of CFH dysfunction remain limited. In this study, we investigated whether extracellular protease-mediated degradation accounts for CFH dysfunction in complement-mediated renal injuries. An unbiased interactome of lupus mice kidneys identified CFH-binding protease. In vitro cleavage assay clarified CFH degradation. Pristane-induced SLE or renal ischemia-reperfusion (I/R) injury models were used in wild-type and ADAMTS7-/- mice. We identified the metalloprotease ADAMTS7 as a CFH-binding protein in lupus kidneys. Moreover, the upregulation of ADAMTS7 correlated with CFH reduction in both lupus mice and patients. Mechanistically, ADAMTS7 is directly bound to CFH complement control protein (CCP) 1-4 domain and degraded CCP 1-7 domain through multiple cleavages. In mice with lupus nephritis or renal I/R injury, ADAMTS7 deficiency alleviated complement activation and related renal pathologies, but without affecting complement-mediated bactericidal activity. Adeno-associated virus-mediated CFH silencing compromised these protective effects of ADAMTS7 knockout against complement-mediated renal injuries in vivo. ADAMTS7-mediated CFH degradation potentiates complement activation and related renal injuries. ADAMTS7 would be a promising anticomplement therapeutic target that does not increase bacterial infection risk.
Sections du résumé
BACKGROUND
The dysfunction of complement factor H (CFH), the main soluble complement negative regulator, potentiates various complement-induced renal injuries. However, insights into the underlying mechanism of CFH dysfunction remain limited. In this study, we investigated whether extracellular protease-mediated degradation accounts for CFH dysfunction in complement-mediated renal injuries.
METHODS
An unbiased interactome of lupus mice kidneys identified CFH-binding protease. In vitro cleavage assay clarified CFH degradation. Pristane-induced SLE or renal ischemia-reperfusion (I/R) injury models were used in wild-type and ADAMTS7-/- mice.
RESULTS
We identified the metalloprotease ADAMTS7 as a CFH-binding protein in lupus kidneys. Moreover, the upregulation of ADAMTS7 correlated with CFH reduction in both lupus mice and patients. Mechanistically, ADAMTS7 is directly bound to CFH complement control protein (CCP) 1-4 domain and degraded CCP 1-7 domain through multiple cleavages. In mice with lupus nephritis or renal I/R injury, ADAMTS7 deficiency alleviated complement activation and related renal pathologies, but without affecting complement-mediated bactericidal activity. Adeno-associated virus-mediated CFH silencing compromised these protective effects of ADAMTS7 knockout against complement-mediated renal injuries in vivo.
CONCLUSION
ADAMTS7-mediated CFH degradation potentiates complement activation and related renal injuries. ADAMTS7 would be a promising anticomplement therapeutic target that does not increase bacterial infection risk.
Identifiants
pubmed: 36735376
doi: 10.1681/ASN.0000000000000004
pii: 00001751-202302000-00015
pmc: PMC10103097
doi:
Substances chimiques
ADAMTS7 Protein
EC 3.4.24.-
Complement Factor H
80295-65-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
291-308Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 by the American Society of Nephrology.
Références
Parente R, Clark SJ, Inforzato A, Day AJ. Complement factor H in host defense and immune evasion. Cell Mol Life Sci. 2017;74(9):1605-1624. doi: 10.1007/s00018-016-2418-4
doi: 10.1007/s00018-016-2418-4
Dragon-Durey MA, Loirat C, Cloarec S, et al. Anti-factor H autoantibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2005;16(2):555-563. doi: 10.1681/ASN.2004050380
doi: 10.1681/ASN.2004050380
Blanc C, Togarsimalemath SK, Chauvet S, et al. Anti-factor H autoantibodies in C3 glomerulopathies and in atypical hemolytic uremic syndrome: one target, two diseases. J Immunol. 2015;194(11):5129-5138. doi: 10.4049/jimmunol.1402770
doi: 10.4049/jimmunol.1402770
Wong EKS, Hallam TM, Brocklebank V, et al. Functional characterization of rare genetic variants in the N-terminus of complement factor H in aHUS, C3G, and AMD. Front Immunol. 2020;11:602284. doi: 10.3389/fimmu.2020.602284
doi: 10.3389/fimmu.2020.602284
Saunders RE, Goodship TH, Zipfel PF, Perkins SJ. An interactive web database of factor H-associated hemolytic uremic syndrome mutations: insights into the structural consequences of disease-associated mutations. Hum Mutat. 2006;27(1):21-30. doi: 10.1002/humu.20268
doi: 10.1002/humu.20268
Raychaudhuri S, Iartchouk O, Chin K, et al. A rare penetrant mutation in CFH confers high risk of age-related macular degeneration. Nat Genet. 2011;43(12):1232-1236. doi: 10.1038/ng.976
doi: 10.1038/ng.976
Moore I, Strain L, Pappworth I, et al. Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood. 2010;115(2):379-387. doi: 10.1182/blood-2009-05-221549
doi: 10.1182/blood-2009-05-221549
Goodship TH, Pappworth IY, Toth T, et al. Factor H autoantibodies in membranoproliferative glomerulonephritis. Mol Immunol. 2012;52(3-4):200-206. doi: 10.1016/j.molimm.2012.05.009
doi: 10.1016/j.molimm.2012.05.009
Makou E, Herbert AP, Barlow PN. Functional anatomy of complement factor H. Biochemistry. 2013;52(23):3949-3962. doi: 10.1021/bi4003452
doi: 10.1021/bi4003452
Renner B, Tong HH, Laskowski J, et al. Annexin A2 enhances complement activation by inhibiting factor H. J Immunol. 2016;196(3):1355-1365. doi: 10.4049/jimmunol.1500793
doi: 10.4049/jimmunol.1500793
Stravalaci M, Davi F, Parente R, et al. Control of complement activation by the long pentraxin PTX3: implications in age-related macular degeneration. Front Pharmacol. 2020;11:591908. doi: 10.3389/fphar.2020.591908
doi: 10.3389/fphar.2020.591908
Wang FM, Song D, Pang Y, Song Y, Yu F, Zhao MH. The dysfunctions of complement factor H in lupus nephritis. Lupus. 2016;25(12):1328-1340. doi: 10.1177/0961203316642307
doi: 10.1177/0961203316642307
Wang FM, Yu F, Tan Y, Song D, Zhao MH. Serum complement factor H is associated with clinical and pathological activities of patients with lupus nephritis. Rheumatology (Oxford). 2012;51(12):2269-2277. doi: 10.1093/rheumatology/kes218
doi: 10.1093/rheumatology/kes218
Thurman JM, Ljubanovic D, Royer PA, et al. Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion. J Clin Invest. 2006;116(2):357-368. doi: 10.1172/jci24521
doi: 10.1172/jci24521
Bao L, Haas M, Quigg RJ. Complement factor H deficiency accelerates development of lupus nephritis. J Am Soc Nephrol. 2011;22(2):285-295. doi: 10.1681/ASN.2010060647
doi: 10.1681/ASN.2010060647
Blaum BS, Hannan JP, Herbert AP, Kavanagh D, Uhrin D, Stehle T. Structural basis for sialic acid-mediated self-recognition by complement factor H. Nat Chem Biol. 2015;11(1):77-82. doi: 10.1038/nchembio.1696
doi: 10.1038/nchembio.1696
Dong Y, Zhao H, Man J, Fu S, Yang L. MMP-9-mediated regulation of hypoxia- reperfusion injury-related neutrophil inflammation in an in vitro proximal tubular cell model. Ren Fail. 2021;43(1):900-910. doi: 10.1080/0886022x.2021.1930558
doi: 10.1080/0886022x.2021.1930558
Wei R, Gao B, Shih F, et al. Alterations in urinary collagen peptides in lupus nephritis subjects correlate with renal dysfunction and renal histopathology. Nephrol Dial Transplant. 2017;32(9):1468-1477. doi: 10.1093/ndt/gfw446
doi: 10.1093/ndt/gfw446
Kessler T, Zhang L, Liu Z, et al. ADAMTS-7 inhibits re-endothelialization of injured arteries and promotes vascular remodeling through cleavage of thrombospondin-1. Circulation. 2015;131(13):1191-1201. doi: 10.1161/circulationaha.114.014072
doi: 10.1161/circulationaha.114.014072
Liu M, Wang Y, Wang F, et al. Interaction of uromodulin and complement factor H enhances C3b inactivation. J Cell Mol Med. 2016;20(10):1821-1828. doi: 10.1111/jcmm.12872
doi: 10.1111/jcmm.12872
Li LL, Tan Y, Song D, et al. Anti-complement factor H autoantibodies may be protective in lupus nephritis. Clin Chim Acta. 2020;508:1-8. doi: 10.1016/j.cca.2020.05.005
doi: 10.1016/j.cca.2020.05.005
Liu CJ, Kong W, Ilalov K, et al. ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. FASEB J. 2006;20(7):988-990. doi: 10.1096/fj.05-3877fje
doi: 10.1096/fj.05-3877fje
Pouw RB, Brouwer MC, de Gast M, et al. Potentiation of complement regulator factor H protects human endothelial cells from complement attack in aHUS sera. Blood Adv. 2019;3(4):621-632. doi: 10.1182/bloodadvances.2018025692
doi: 10.1182/bloodadvances.2018025692
Wang FM, Yu F, Zhao MH. A method of purifying intact complement factor H from human plasma. Protein Expr Purif. 2013;91(2):105-111. doi: 10.1016/j.pep.2013.07.014
doi: 10.1016/j.pep.2013.07.014
Kikawada E, Lenda DM, Kelley VR. IL-12 deficiency in MRL- Faslpr mice delays nephritis and intrarenal IFN-γ expression, and diminishes systemic pathology. J Immunol. 2003;170(7):3915-3925. doi: 10.4049/jimmunol.170.7.3915
doi: 10.4049/jimmunol.170.7.3915
Lenda DM, Stanley ER, Kelley VR. Negative role of colony-stimulating factor-1 in macrophage, T cell, and B cell mediated autoimmune disease in MRL- Faslpr mice. J Immunol. 2004;173(7):4744-4754. doi: 10.4049/jimmunol.173.7.4744
doi: 10.4049/jimmunol.173.7.4744
Arai S, Kitada K, Yamazaki T, et al. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice. Nat Med. 2016;22(2):183-193. doi: 10.1038/nm.4012
doi: 10.1038/nm.4012
Broekema M, Harmsen MC, Koerts JA, et al. Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats. Kidney Int. 2005;68(6):2572-2581. doi: 10.1111/j.1523-1755.2005.00728.x
doi: 10.1111/j.1523-1755.2005.00728.x
Leffler J, Bengtsson AA, Blom AM. The complement system in systemic lupus erythematosus: an update. Ann Rheum Dis. 2014;73(9):1601-1606. doi: 10.1136/annrheumdis-2014-205287
doi: 10.1136/annrheumdis-2014-205287
Alexander JJ, Wang Y, Chang A, et al. Mouse podocyte complement factor H: the functional analog to human complement receptor 1. J Am Soc Nephrol. 2007;18(4):1157-1166. doi: 10.1681/ASN.2006101125
doi: 10.1681/ASN.2006101125
Danobeitia JS, Djamali A, Fernandez LA. The role of complement in the pathogenesis of renal ischemia-reperfusion injury and fibrosis. Fibrogenesis Tissue Repair. 2014;7(1):16. doi: 10.1186/1755-1536-7-16
doi: 10.1186/1755-1536-7-16
Wang L, Zheng J, Bai X, et al. ADAMTS-7 mediates vascular smooth muscle cell migration and neointima formation in balloon-injured rat arteries. Circ Res. 2009;104(5):688-698. doi: 10.1161/circresaha.108.188425
doi: 10.1161/circresaha.108.188425
Pannu N, Bhatnagar A. Oxidative stress and immune complexes: pathogenic mechanisms in pristane induced murine model of lupus. Immunobiology. 2020;225(1):151871. doi: 10.1016/j.imbio.2019.11.006
doi: 10.1016/j.imbio.2019.11.006
Kahlenberg JM, Yalavarthi S, Zhao W, et al. An essential role of caspase 1 in the induction of murine lupus and its associated vascular damage. Arthritis Rheumatol. 2014;66:152-162. doi: 10.1002/art.38225
doi: 10.1002/art.38225
Nazir S, Gadi I, Al-Dabet MM, et al. Cytoprotective activated protein C averts Nlrp3 inflammasome- induced ischemia-reperfusion injury via mTORC1 inhibition. Blood. 2017;130(24):2664-2677. doi: 10.1182/blood-2017-05-782102
doi: 10.1182/blood-2017-05-782102
Ke J, Zhao F, Luo Y, Deng F, Wu X. MiR-124 negatively regulated PARP1 to alleviate renal ischemia-reperfusion injury by inhibiting TNFα/RIP1/RIP3 pathway. Int J Biol Sci. 2021;17(8):2099-2111. doi: 10.7150/ijbs.58163
doi: 10.7150/ijbs.58163
Zhao M, Wang Y, Li L, et al. Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance. Theranostics. 2021;11(4):1845-1863. doi: 10.7150/thno.50905
doi: 10.7150/thno.50905
Wong EKS, Kavanagh D. Diseases of complement dysregulation-an overview. Semin Immunopathol. 2018;40(1):49-64. doi: 10.1007/s00281-017-0663-8
doi: 10.1007/s00281-017-0663-8
Wang L, Cano M, Datta S, et al. Pentraxin 3 recruits complement factor H to protect against oxidative stress-induced complement and inflammasome overactivation. J Pathol. 2016;240(4):495-506. doi: 10.1002/path.4811
doi: 10.1002/path.4811
Kopp A, Hebecker M, Svobodova E, Jozsi M. Factor h: a complement regulator in health and disease, and a mediator of cellular interactions. Biomolecules. 2012;2(1):46-75. doi: 10.3390/biom2010046
doi: 10.3390/biom2010046
Jozsi M, Oppermann M, Lambris JD, Zipfel PF. The C-terminus of complement factor H is essential for host cell protection. Mol Immunol. 2007;44(10):2697-2706. doi: 10.1016/j.molimm.2006.12.001
doi: 10.1016/j.molimm.2006.12.001
Reilly MP, Li M, He J, et al. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011;377(9763):383-392. doi: 10.1016/s0140-6736(10)61996-4
doi: 10.1016/s0140-6736(10)61996-4
Lai Y, Bai X, Zhao Y, et al. ADAMTS-7 forms a positive feedback loop with TNF-alpha in the pathogenesis of osteoarthritis. Ann Rheum Dis. 2014;73(8):1575-1584. doi: 10.1136/annrheumdis-2013-203561
doi: 10.1136/annrheumdis-2013-203561
Puy C, Pang J, Reitsma SE, et al. Cross-talk between the complement pathway and the contact activation system of coagulation: activated factor XI neutralizes complement factor H. J Immunol. 2021;206(8):1784-1792. doi: 10.4049/jimmunol.2000398
doi: 10.4049/jimmunol.2000398
Sciascia S, Radin M, Yazdany J, et al. Expanding the therapeutic options for renal involvement in lupus: eculizumab, available evidence. Rheumatol Int. 2017;37(8):1249-1255. doi: 10.1007/s00296-017-3686-5
doi: 10.1007/s00296-017-3686-5
Nurnberger J, Philipp T, Witzke O, et al. Eculizumab for atypical hemolytic- uremic syndrome. N Engl J Med. 2009;360(5):542-544. doi: 10.1056/nejmc0808527
doi: 10.1056/nejmc0808527
Welte T, Arnold F, Kappes J, et al. Treating C3 glomerulopathy with eculizumab. BMC Nephrol. 2018;19(1):7. doi: 10.1186/s12882-017-0802-4
doi: 10.1186/s12882-017-0802-4
Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355(12):1233-1243. doi: 10.1056/nejmoa061648
doi: 10.1056/nejmoa061648
Ricklin D, Mastellos DC, Reis ES, Lambris JD. The renaissance of complement therapeutics. Nat Rev Nephrol. 2018;14(1):26-47. doi: 10.1038/nrneph.2017.156
doi: 10.1038/nrneph.2017.156
Harris CL, Pouw RB, Kavanagh D, Sun R, Ricklin D. Developments in anti- complement therapy; from disease to clinical trial. Mol Immunol. 2018;102:89-119. doi: 10.1016/j.molimm.2018.06.008
doi: 10.1016/j.molimm.2018.06.008
Harder MJ, Anliker M, Hochsmann B, et al. Comparative analysis of novel complement-targeted inhibitors, MiniFH, and the natural regulators factor H and factor H- like protein 1 reveal functional determinants of complement regulation. J Immunol. 2016;196(2):866-876. doi: 10.4049/jimmunol.1501919
doi: 10.4049/jimmunol.1501919
Gavriilaki E, Brodsky RA. Complementopathies and precision medicine. J Clin Invest. 2020;130(5):2152-2163. doi: 10.1172/jci136094
doi: 10.1172/jci136094