Skip to main content
Top
Published in: Molecular and Cellular Pediatrics 1/2023

Open Access 01-12-2023 | Review

New insights into the immune functions of podocytes: the role of complement

Authors: Valentina Bruno, Anne Katrin Mühlig, Jun Oh, Christoph Licht

Published in: Molecular and Cellular Pediatrics | Issue 1/2023

Login to get access

Abstract

Podocytes are differentiated epithelial cells which play an essential role to ensure a normal function of the glomerular filtration barrier (GFB). In addition to their adhesive properties in maintaining the integrity of the filtration barrier, they have other functions, such as synthesis of components of the glomerular basement membrane (GBM), production of vascular endothelial growth factor (VEGF), release of inflammatory proteins, and expression of complement components. They also participate in the glomerular crosstalk through multiple signalling pathways, including endothelin-1, VEGF, transforming growth factor β (TGFβ), bone morphogenetic protein 7 (BMP-7), latent transforming growth factor β-binding protein 1 (LTBP1), and extracellular vesicles.
Growing literature suggests that podocytes share many properties of innate and adaptive immunity, supporting a multifunctional role ensuring a healthy glomerulus. As consequence, the “immune podocyte” dysfunction is thought to be involved in the pathogenesis of several glomerular diseases, referred to as “podocytopathies.” Multiple factors like mechanical, oxidative, and/or immunologic stressors can induce cell injury. The complement system, as part of both innate and adaptive immunity, can also define podocyte damage by several mechanisms, such as reactive oxygen species (ROS) generation, cytokine production, and endoplasmic reticulum stress, ultimately affecting the integrity of the cytoskeleton, with subsequent podocyte detachment from the GBM and onset of proteinuria.
Interestingly, podocytes are found to be both source and target of complement-mediated injury. Podocytes express complement proteins which contribute to local complement activation. At the same time, they rely on several protective mechanisms to escape this damage. Podocytes express complement factor H (CFH), one of the main regulators of the complement cascade, as well as membrane-bound complement regulators like CD46 or membrane cofactor protein (MCP), CD55 or decay-accelerating factor (DAF), and CD59 or defensin. Further mechanisms, like autophagy or actin-based endocytosis, are also involved to ensure podocyte homeostasis and protection against injury.
This review will provide an overview of the immune functions of podocytes and their response to immune-mediated injury, focusing on the pathogenic link between complement and podocyte damage.
Literature
6.
go back to reference Grahammer F, Schell C, Huber TB (2013) The podocyte slit diaphragm—from a thin grey line to a complex signalling hub. Nat Rev Nephrol 9(10):587–598PubMedCrossRef Grahammer F, Schell C, Huber TB (2013) The podocyte slit diaphragm—from a thin grey line to a complex signalling hub. Nat Rev Nephrol 9(10):587–598PubMedCrossRef
7.
go back to reference St. John PL, Abrahamson DR (2001) Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and -11 chains. Kidney International. 60(3):1037–46PubMedCrossRef St. John PL, Abrahamson DR (2001) Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and -11 chains. Kidney International. 60(3):1037–46PubMedCrossRef
8.
9.
go back to reference Byron A, Randles MJ, Humphries JD, Mironov A, Hamidi H, Harris S et al (2014) Glomerular cell cross-talk influences composition and assembly of extracellular matrix. J Am Soc Nephrol 25(5):953–966PubMedPubMedCentralCrossRef Byron A, Randles MJ, Humphries JD, Mironov A, Hamidi H, Harris S et al (2014) Glomerular cell cross-talk influences composition and assembly of extracellular matrix. J Am Soc Nephrol 25(5):953–966PubMedPubMedCentralCrossRef
12.
go back to reference Banas MC, Banas B, Hudkins KL, Wietecha TA, Iyoda M, Bock E et al (2008) TLR4 links podocytes with the innate immune system to mediate glomerular injury. J Am Soc Nephrol 19(4):704–713PubMedPubMedCentralCrossRef Banas MC, Banas B, Hudkins KL, Wietecha TA, Iyoda M, Bock E et al (2008) TLR4 links podocytes with the innate immune system to mediate glomerular injury. J Am Soc Nephrol 19(4):704–713PubMedPubMedCentralCrossRef
14.
go back to reference Goldwich A, Burkard M, Ölke M, Daniel C, Amann K, Hugo C et al (2013) Podocytes are nonhematopoietic professional antigen-presenting cells. J Am Soc Nephrol 24(6):906–916PubMedPubMedCentralCrossRef Goldwich A, Burkard M, Ölke M, Daniel C, Amann K, Hugo C et al (2013) Podocytes are nonhematopoietic professional antigen-presenting cells. J Am Soc Nephrol 24(6):906–916PubMedPubMedCentralCrossRef
15.
go back to reference Li S, Liu Y, He Y, Rong W, Zhang M, Li L et al (2020) Podocytes present antigen to activate specific T cell immune responses in inflammatory renal disease. J Pathol 252(2):165–177PubMedCrossRef Li S, Liu Y, He Y, Rong W, Zhang M, Li L et al (2020) Podocytes present antigen to activate specific T cell immune responses in inflammatory renal disease. J Pathol 252(2):165–177PubMedCrossRef
17.
go back to reference Mühlig AK, Keir LS, Abt JC, Heidelbach HS, Horton R, Welsh GI, et al (2020) Podocytes produce and secrete functional complement C3 and complement factor H. Front Immunol 11:1833 Mühlig AK, Keir LS, Abt JC, Heidelbach HS, Horton R, Welsh GI, et al (2020) Podocytes produce and secrete functional complement C3 and complement factor H. Front Immunol 11:1833
18.
go back to reference Angeletti A, Cantarelli C, Petrosyan A, Andrighetto S, Budge K, D'Agati VD, et al (2020) Loss of decay-accelerating factor triggers podocyte injury and glomerulosclerosis. J Exp Med 217(9):e20191699 Angeletti A, Cantarelli C, Petrosyan A, Andrighetto S, Budge K, D'Agati VD, et al (2020) Loss of decay-accelerating factor triggers podocyte injury and glomerulosclerosis. J Exp Med 217(9):e20191699
19.
go back to reference Kopp JB, Anders H-J, Susztak K, Podestà MA, Remuzzi G, Hildebrandt F, et al (2020) Podocytopathies. Nat Rev Dis Prim 6(1):68 Kopp JB, Anders H-J, Susztak K, Podestà MA, Remuzzi G, Hildebrandt F, et al (2020) Podocytopathies. Nat Rev Dis Prim 6(1):68
20.
go back to reference Wiggins R-C (2007) The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 71(12):1205–1214PubMedCrossRef Wiggins R-C (2007) The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 71(12):1205–1214PubMedCrossRef
21.
go back to reference Huang J, Cui Z, Gu Q-H, Zhang Y-M, Qu Z, Wang X et al (2020) Complement activation profile of patients with primary focal segmental glomerulosclerosis. PLoS ONE 15(6):e0234934PubMedPubMedCentralCrossRef Huang J, Cui Z, Gu Q-H, Zhang Y-M, Qu Z, Wang X et al (2020) Complement activation profile of patients with primary focal segmental glomerulosclerosis. PLoS ONE 15(6):e0234934PubMedPubMedCentralCrossRef
22.
go back to reference Couser WG (2012) Basic and translational concepts of immune-mediated glomerular diseases. J Am Soc Nephrol 23(3):381–399PubMedCrossRef Couser WG (2012) Basic and translational concepts of immune-mediated glomerular diseases. J Am Soc Nephrol 23(3):381–399PubMedCrossRef
23.
go back to reference Maillard N, Wyatt RJ, Julian BA, Kiryluk K, Gharavi A, Fremeaux-Bacchi V et al (2015) Current understanding of the role of complement in IgA nephropathy. J Am Soc Nephrol 26(7):1503–1512PubMedPubMedCentralCrossRef Maillard N, Wyatt RJ, Julian BA, Kiryluk K, Gharavi A, Fremeaux-Bacchi V et al (2015) Current understanding of the role of complement in IgA nephropathy. J Am Soc Nephrol 26(7):1503–1512PubMedPubMedCentralCrossRef
24.
go back to reference Kawasaki T, Kawai T (2014) Toll-like receptor signaling pathways. Front Immunol 5:461 Kawasaki T, Kawai T (2014) Toll-like receptor signaling pathways. Front Immunol 5:461
25.
go back to reference Karikó K, Ni H, Capodici J, Lamphier M, Weissman D (2004) mRNA is an endogenous ligand for toll-like receptor 3. J Biol Chem 279(13):12542–12550PubMedCrossRef Karikó K, Ni H, Capodici J, Lamphier M, Weissman D (2004) mRNA is an endogenous ligand for toll-like receptor 3. J Biol Chem 279(13):12542–12550PubMedCrossRef
26.
go back to reference Srivastava T, Sharma M, Yew K-H, Sharma R, Duncan RS, Saleem MA et al (2013) LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile. J Cell Commun Signal 7(1):49–60PubMedCrossRef Srivastava T, Sharma M, Yew K-H, Sharma R, Duncan RS, Saleem MA et al (2013) LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile. J Cell Commun Signal 7(1):49–60PubMedCrossRef
27.
go back to reference Bao W, Xia H, Liang Y, Ye Y, Lu Y, Xu X et al (2016) Toll-like receptor 9 can be activated by endogenous mitochondrial DNA to induce podocyte apoptosis. Sci Rep 6(1):22579PubMedPubMedCentralCrossRef Bao W, Xia H, Liang Y, Ye Y, Lu Y, Xu X et al (2016) Toll-like receptor 9 can be activated by endogenous mitochondrial DNA to induce podocyte apoptosis. Sci Rep 6(1):22579PubMedPubMedCentralCrossRef
28.
go back to reference Coers W, Brouwer L, Vos JTWM, Chand A, Huitema S, Heeringa P et al (2008) Podocyte expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1) in experimental pauci-immune crescentic glomerulonephritis. Clin Exp Immunol 98(2):279–286CrossRef Coers W, Brouwer L, Vos JTWM, Chand A, Huitema S, Heeringa P et al (2008) Podocyte expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1) in experimental pauci-immune crescentic glomerulonephritis. Clin Exp Immunol 98(2):279–286CrossRef
29.
go back to reference Baudeau C, Delarue F, Hé CJ, Nguyen G, Adida C, Peraldi MN et al (1994) Induction of MHC class II molecules HLA-DR, -DP and -DQ and ICAM 1 in human podocytes by gamma-interferon. Exp Nephrol 2(5):306–312PubMed Baudeau C, Delarue F, Hé CJ, Nguyen G, Adida C, Peraldi MN et al (1994) Induction of MHC class II molecules HLA-DR, -DP and -DQ and ICAM 1 in human podocytes by gamma-interferon. Exp Nephrol 2(5):306–312PubMed
30.
go back to reference Reiser J, Von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L et al (2004) Induction of B7–1 in podocytes is associated with nephrotic syndrome. J Clin Investig 113(10):1390–1397PubMedPubMedCentralCrossRef Reiser J, Von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L et al (2004) Induction of B7–1 in podocytes is associated with nephrotic syndrome. J Clin Investig 113(10):1390–1397PubMedPubMedCentralCrossRef
31.
go back to reference Akilesh S, Huber TB, Wu H, Wang G, Hartleben B, Kopp JB et al (2008) Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proc Natl Acad Sci 105(3):967–972PubMedPubMedCentralCrossRef Akilesh S, Huber TB, Wu H, Wang G, Hartleben B, Kopp JB et al (2008) Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proc Natl Acad Sci 105(3):967–972PubMedPubMedCentralCrossRef
32.
go back to reference Dylewski J, Dobrinskikh E, Lewis L, Tonsawan P, Miyazaki M, Jat PS et al (2019) Differential trafficking of albumin and IgG facilitated by the neonatal Fc receptor in podocytes in vitro and in vivo. PLoS ONE 14(2):e0209732PubMedPubMedCentralCrossRef Dylewski J, Dobrinskikh E, Lewis L, Tonsawan P, Miyazaki M, Jat PS et al (2019) Differential trafficking of albumin and IgG facilitated by the neonatal Fc receptor in podocytes in vitro and in vivo. PLoS ONE 14(2):e0209732PubMedPubMedCentralCrossRef
33.
go back to reference Bariéty J, Nochy D, Mandet C, Jacquot C, Glotz D, Meyrier A (1998) Podocytes undergo phenotypic changes and express macrophagic-associated markers in idiopathic collapsing glomerulopathy. Kidney Int 53(4):918–925PubMedCrossRef Bariéty J, Nochy D, Mandet C, Jacquot C, Glotz D, Meyrier A (1998) Podocytes undergo phenotypic changes and express macrophagic-associated markers in idiopathic collapsing glomerulopathy. Kidney Int 53(4):918–925PubMedCrossRef
34.
go back to reference Mendrick DL, Kelly DM, Rennke HG (1991) Antigen processing and presentation by glomerular visceral epithelium in vitro. Kidney Int 39(1):71–78PubMedCrossRef Mendrick DL, Kelly DM, Rennke HG (1991) Antigen processing and presentation by glomerular visceral epithelium in vitro. Kidney Int 39(1):71–78PubMedCrossRef
35.
go back to reference Burt D, Salvidio G, Tarabra E, Barutta F, Pinach S, Dentelli P et al (2007) The monocyte chemoattractant protein-1/cognate CC chemokine receptor 2 system affects cell motility in cultured human podocytes. Am J Pathol 171(6):1789–1799PubMedPubMedCentralCrossRef Burt D, Salvidio G, Tarabra E, Barutta F, Pinach S, Dentelli P et al (2007) The monocyte chemoattractant protein-1/cognate CC chemokine receptor 2 system affects cell motility in cultured human podocytes. Am J Pathol 171(6):1789–1799PubMedPubMedCentralCrossRef
36.
go back to reference Huber TB, Reinhardt HC, Exner M, Burger JA, Kerjaschki D, Saleem MA et al (2002) Expression of functional CCR and CXCR chemokine receptors in podocytes. J Immunol 168(12):6244–6252PubMedCrossRef Huber TB, Reinhardt HC, Exner M, Burger JA, Kerjaschki D, Saleem MA et al (2002) Expression of functional CCR and CXCR chemokine receptors in podocytes. J Immunol 168(12):6244–6252PubMedCrossRef
37.
go back to reference Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354(6):610–621PubMedCrossRef Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354(6):610–621PubMedCrossRef
39.
go back to reference Griffith JW, Sokol CL, Luster AD (2014) Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol 32(1):659–702PubMedCrossRef Griffith JW, Sokol CL, Luster AD (2014) Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol 32(1):659–702PubMedCrossRef
40.
go back to reference Niemir ZI, Stein H, Dworacki G, Mundel P, Koehl N, Koch B et al (1997) Podocytes are the major source of IL-1 alpha and IL-1 beta in human glomerulonephritides. Kidney Int 52(2):393–403PubMedCrossRef Niemir ZI, Stein H, Dworacki G, Mundel P, Koehl N, Koch B et al (1997) Podocytes are the major source of IL-1 alpha and IL-1 beta in human glomerulonephritides. Kidney Int 52(2):393–403PubMedCrossRef
41.
go back to reference Wright RD, Beresford MW (2018) Podocytes contribute, and respond, to the inflammatory environment in lupus nephritis. American Journal of Physiology-Renal Physiology 315(6):F1683–F1694PubMedPubMedCentralCrossRef Wright RD, Beresford MW (2018) Podocytes contribute, and respond, to the inflammatory environment in lupus nephritis. American Journal of Physiology-Renal Physiology 315(6):F1683–F1694PubMedPubMedCentralCrossRef
42.
go back to reference Xiong W, Meng X-F, Zhang C (2020) Inflammasome activation in podocytes: a new mechanism of glomerular diseases. Inflamm Res 69(8):731–743PubMedCrossRef Xiong W, Meng X-F, Zhang C (2020) Inflammasome activation in podocytes: a new mechanism of glomerular diseases. Inflamm Res 69(8):731–743PubMedCrossRef
43.
go back to reference Zoshima T, Hara S, Yamagishi M, Pastan I, Matsusaka T, Kawano M, et al (2019) Possible role of complement factor H in podocytes in clearing glomerular subendothelial immune complex deposits. Sci Rep 9(1):7857 Zoshima T, Hara S, Yamagishi M, Pastan I, Matsusaka T, Kawano M, et al (2019) Possible role of complement factor H in podocytes in clearing glomerular subendothelial immune complex deposits. Sci Rep 9(1):7857
44.
go back to reference Tipping PG (2008) Are podocytes passive or provocative in proteinuric glomerular pathology? J Am Soc Nephrol 19(4):651–653PubMedCrossRef Tipping PG (2008) Are podocytes passive or provocative in proteinuric glomerular pathology? J Am Soc Nephrol 19(4):651–653PubMedCrossRef
45.
go back to reference Luo W, Olaru F, Miner JH, Beck LH, van der Vlag J, Thurman JM et al (2018) Alternative pathway is essential for glomerular complement activation and proteinuria in a mouse model of membranous nephropathy. Front Immunol 9:1433PubMedPubMedCentralCrossRef Luo W, Olaru F, Miner JH, Beck LH, van der Vlag J, Thurman JM et al (2018) Alternative pathway is essential for glomerular complement activation and proteinuria in a mouse model of membranous nephropathy. Front Immunol 9:1433PubMedPubMedCentralCrossRef
46.
go back to reference Dunkelberger JR, Song W-C (2010) Complement and its role in innate and adaptive immune responses. Cell Res 20(1):34–50PubMedCrossRef Dunkelberger JR, Song W-C (2010) Complement and its role in innate and adaptive immune responses. Cell Res 20(1):34–50PubMedCrossRef
48.
50.
51.
go back to reference Zipfel PF, Skerka C (2009) Complement regulators and inhibitory proteins. Nat Rev Immunol 9(10):729–740PubMedCrossRef Zipfel PF, Skerka C (2009) Complement regulators and inhibitory proteins. Nat Rev Immunol 9(10):729–740PubMedCrossRef
52.
go back to reference Takano T, Elimam H, Cybulsky AV (2013) Complement-mediated cellular injury. Semin Nephrol 33(6):586–601PubMedCrossRef Takano T, Elimam H, Cybulsky AV (2013) Complement-mediated cellular injury. Semin Nephrol 33(6):586–601PubMedCrossRef
54.
go back to reference Cybulsky AV, Quigg RJ, Salant DJ (2005) Experimental membranous nephropathy redux. Am J Physiol Renal Physiol 289(4):F660–F671PubMedCrossRef Cybulsky AV, Quigg RJ, Salant DJ (2005) Experimental membranous nephropathy redux. Am J Physiol Renal Physiol 289(4):F660–F671PubMedCrossRef
55.
go back to reference Tegla CA, Cudrici C, Patel S, Trippe R, Rus V, Niculescu F et al (2011) Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol Res 51(1):45–60PubMedPubMedCentralCrossRef Tegla CA, Cudrici C, Patel S, Trippe R, Rus V, Niculescu F et al (2011) Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol Res 51(1):45–60PubMedPubMedCentralCrossRef
57.
go back to reference Cybulsky AV, Bonventre JV, Quigg RJ, Lieberthal W, Salant DJ (1990) Cytosolic calcium and protein kinase C reduce complement-mediated glomerular epithelial injury. Kidney Int 38(5):803–811PubMedCrossRef Cybulsky AV, Bonventre JV, Quigg RJ, Lieberthal W, Salant DJ (1990) Cytosolic calcium and protein kinase C reduce complement-mediated glomerular epithelial injury. Kidney Int 38(5):803–811PubMedCrossRef
58.
go back to reference Carney DF, Lang TJ, Shin ML (1990) Multiple signal messengers generated by terminal complement complexes and their role in terminal complement complex elimination. J Immunol 145(2):623–629PubMedCrossRef Carney DF, Lang TJ, Shin ML (1990) Multiple signal messengers generated by terminal complement complexes and their role in terminal complement complex elimination. J Immunol 145(2):623–629PubMedCrossRef
59.
go back to reference Zhang L, Ji T, Wang Q, Meng K, Zhang R, Yang H et al (2017) Calcium-sensing receptor stimulation in cultured glomerular podocytes induces TRPC6-dependent calcium entry and RhoA activation. Cell Physiol Biochem 43(5):1777–1789PubMedCrossRef Zhang L, Ji T, Wang Q, Meng K, Zhang R, Yang H et al (2017) Calcium-sensing receptor stimulation in cultured glomerular podocytes induces TRPC6-dependent calcium entry and RhoA activation. Cell Physiol Biochem 43(5):1777–1789PubMedCrossRef
60.
go back to reference Kistler AD, Singh G, Altintas MM, Yu H, Fernandez IC, Gu C et al (2013) Transient receptor potential channel 6 (TRPC6) protects podocytes during complement-mediated glomerular disease. J Biol Chem 288(51):36598–36609PubMedPubMedCentralCrossRef Kistler AD, Singh G, Altintas MM, Yu H, Fernandez IC, Gu C et al (2013) Transient receptor potential channel 6 (TRPC6) protects podocytes during complement-mediated glomerular disease. J Biol Chem 288(51):36598–36609PubMedPubMedCentralCrossRef
62.
go back to reference Cybulsky AV, Takano T, Papillon J, Mctavish AJ (2000) Complement-induced phospholipase A2 activation in experimental membranous nephropathy1 See Editorial by Shankland, p. 1204. Kidney Int. 57(3):1052–62PubMedCrossRef Cybulsky AV, Takano T, Papillon J, Mctavish AJ (2000) Complement-induced phospholipase A2 activation in experimental membranous nephropathy1 See Editorial by Shankland, p. 1204. Kidney Int. 57(3):1052–62PubMedCrossRef
63.
64.
go back to reference Neale TJ, Ojha PP, Exner M, Poczewski H, Rüger B, Witztum JL et al (1994) Proteinuria in passive Heymann nephritis is associated with lipid peroxidation and formation of adducts on type IV collagen. J Clin Investig 94(4):1577–1584PubMedPubMedCentralCrossRef Neale TJ, Ojha PP, Exner M, Poczewski H, Rüger B, Witztum JL et al (1994) Proteinuria in passive Heymann nephritis is associated with lipid peroxidation and formation of adducts on type IV collagen. J Clin Investig 94(4):1577–1584PubMedPubMedCentralCrossRef
65.
go back to reference Cybulsky AV (2013) The intersecting roles of endoplasmic reticulum stress, ubiquitin–proteasome system, and autophagy in the pathogenesis of proteinuric kidney disease. Kidney Int 84(1):25–33PubMedCrossRef Cybulsky AV (2013) The intersecting roles of endoplasmic reticulum stress, ubiquitin–proteasome system, and autophagy in the pathogenesis of proteinuric kidney disease. Kidney Int 84(1):25–33PubMedCrossRef
66.
go back to reference Pippin JW, Durvasula R, Petermann A, Hiromura K, Couser WG, Shankland SJ (2003) DNA damage is a novel response to sublytic complement C5b–9–induced injury in podocytes. J Clin Invest. 111(6):877–85PubMedPubMedCentralCrossRef Pippin JW, Durvasula R, Petermann A, Hiromura K, Couser WG, Shankland SJ (2003) DNA damage is a novel response to sublytic complement C5b–9–induced injury in podocytes. J Clin Invest. 111(6):877–85PubMedPubMedCentralCrossRef
67.
go back to reference Brinkkoetter PT, Bork T, Salou S, Liang W, Mizi A, Özel C et al (2019) Anaerobic glycolysis maintains the glomerular filtration barrier independent of mitochondrial metabolism and dynamics. Cell Rep 27(5):1551–66.e5PubMedPubMedCentralCrossRef Brinkkoetter PT, Bork T, Salou S, Liang W, Mizi A, Özel C et al (2019) Anaerobic glycolysis maintains the glomerular filtration barrier independent of mitochondrial metabolism and dynamics. Cell Rep 27(5):1551–66.e5PubMedPubMedCentralCrossRef
68.
go back to reference Topham PS, Haydar SA, Kuphal R, Lightfoot JD, Salant DJ (1999) Complement-mediated injury reversibly disrupts glomerular epithelial cell actin microfilaments and focal adhesions. Kidney Int 55(5):1763–1775PubMedCrossRef Topham PS, Haydar SA, Kuphal R, Lightfoot JD, Salant DJ (1999) Complement-mediated injury reversibly disrupts glomerular epithelial cell actin microfilaments and focal adhesions. Kidney Int 55(5):1763–1775PubMedCrossRef
69.
go back to reference Lv Q, Yang F, Chen K, Zhang Y (2016) Autophagy protects podocytes from sublytic complement induced injury. Exp Cell Res 341(2):132–138PubMedCrossRef Lv Q, Yang F, Chen K, Zhang Y (2016) Autophagy protects podocytes from sublytic complement induced injury. Exp Cell Res 341(2):132–138PubMedCrossRef
70.
go back to reference Liu WJ, Li Z-H, Chen X-C, Zhao X-L, Zhong Z, Yang C, et al (2017) Blockage of the lysosome-dependent autophagic pathway contributes to complement membrane attack complex-induced podocyte injury in idiopathic membranous nephropathy. Sci Rep 7(1):8643 Liu WJ, Li Z-H, Chen X-C, Zhao X-L, Zhong Z, Yang C, et al (2017) Blockage of the lysosome-dependent autophagic pathway contributes to complement membrane attack complex-induced podocyte injury in idiopathic membranous nephropathy. Sci Rep 7(1):8643
71.
go back to reference Keir LS, Firth R, Aponik L, Feitelberg D, Sakimoto S, Aguilar E et al (2016) VEGF regulates local inhibitory complement proteins in the eye and kidney. J Clin Investig 127(1):199–214PubMedPubMedCentralCrossRef Keir LS, Firth R, Aponik L, Feitelberg D, Sakimoto S, Aguilar E et al (2016) VEGF regulates local inhibitory complement proteins in the eye and kidney. J Clin Investig 127(1):199–214PubMedPubMedCentralCrossRef
72.
go back to reference Medica D, Franzin R, Stasi A, Castellano G, Migliori M, Panichi V et al (2021) Extracellular vesicles derived from endothelial progenitor cells protect human glomerular endothelial cells and podocytes from complement- and cytokine-mediated injury. Cells 10(7):1675PubMedPubMedCentralCrossRef Medica D, Franzin R, Stasi A, Castellano G, Migliori M, Panichi V et al (2021) Extracellular vesicles derived from endothelial progenitor cells protect human glomerular endothelial cells and podocytes from complement- and cytokine-mediated injury. Cells 10(7):1675PubMedPubMedCentralCrossRef
73.
go back to reference Kaartinen K, Safa A, Kotha S, Ratti G, Meri S (2019) Complement dysregulation in glomerulonephritis. Semin Immunol 45:101331PubMedCrossRef Kaartinen K, Safa A, Kotha S, Ratti G, Meri S (2019) Complement dysregulation in glomerulonephritis. Semin Immunol 45:101331PubMedCrossRef
74.
go back to reference Noris M, Mescia F, Remuzzi G (2012) STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 8(11):622–633PubMedCrossRef Noris M, Mescia F, Remuzzi G (2012) STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 8(11):622–633PubMedCrossRef
75.
76.
go back to reference Birmingham DJ, Hebert LA (2015) The complement system in lupus nephritis. Semin Nephrol 35(5):444–454PubMedCrossRef Birmingham DJ, Hebert LA (2015) The complement system in lupus nephritis. Semin Nephrol 35(5):444–454PubMedCrossRef
77.
go back to reference Holers VM, Banda NK (2018) Complement in the initiation and evolution of rheumatoid arthritis. Front Immunol 9:1057 Holers VM, Banda NK (2018) Complement in the initiation and evolution of rheumatoid arthritis. Front Immunol 9:1057
78.
go back to reference Stites E, Le Quintrec M, Thurman JM (2015) The complement system and antibody-mediated transplant rejection. J Immunol 195(12):5525–5531PubMedCrossRef Stites E, Le Quintrec M, Thurman JM (2015) The complement system and antibody-mediated transplant rejection. J Immunol 195(12):5525–5531PubMedCrossRef
79.
go back to reference McHarg S, Clark SJ, Day AJ, Bishop PN (2015) Age-related macular degeneration and the role of the complement system. Mol Immunol 67(1):43–50PubMedCrossRef McHarg S, Clark SJ, Day AJ, Bishop PN (2015) Age-related macular degeneration and the role of the complement system. Mol Immunol 67(1):43–50PubMedCrossRef
80.
go back to reference Assady S, Wanner N, Skorecki KL, Huber TB (2017) New insights into podocyte biology in glomerular health and disease. J Am Soc Nephrol 28(6):1707–1715PubMedPubMedCentralCrossRef Assady S, Wanner N, Skorecki KL, Huber TB (2017) New insights into podocyte biology in glomerular health and disease. J Am Soc Nephrol 28(6):1707–1715PubMedPubMedCentralCrossRef
81.
83.
go back to reference Zoja C, Buelli S, Morigi M (2019) Shiga toxin triggers endothelial and podocyte injury: the role of complement activation. Pediatr Nephrol 34(3):379–388PubMedCrossRef Zoja C, Buelli S, Morigi M (2019) Shiga toxin triggers endothelial and podocyte injury: the role of complement activation. Pediatr Nephrol 34(3):379–388PubMedCrossRef
84.
go back to reference dos Santos M, Poletti PT, Milhoransa P, Monticielo OA, Veronese FV (2017) Unraveling the podocyte injury in lupus nephritis: clinical and experimental approaches. Semin Arthritis Rheum 46(5):632–641PubMedCrossRef dos Santos M, Poletti PT, Milhoransa P, Monticielo OA, Veronese FV (2017) Unraveling the podocyte injury in lupus nephritis: clinical and experimental approaches. Semin Arthritis Rheum 46(5):632–641PubMedCrossRef
86.
go back to reference Sharma M, Vignesh P, Tiewsoh K, Rawat A (2020) Revisiting the complement system in systemic lupus erythematosus. Expert Rev Clin Immunol 16(4):397–408PubMedCrossRef Sharma M, Vignesh P, Tiewsoh K, Rawat A (2020) Revisiting the complement system in systemic lupus erythematosus. Expert Rev Clin Immunol 16(4):397–408PubMedCrossRef
88.
go back to reference Ronco P, Debiec H (2020) Molecular pathogenesis of membranous nephropathy. Annu Rev Pathol 15:287–313PubMedCrossRef Ronco P, Debiec H (2020) Molecular pathogenesis of membranous nephropathy. Annu Rev Pathol 15:287–313PubMedCrossRef
89.
go back to reference Ronco P, Plaisier E, Debiec H (2021) Advances in membranous nephropathy. J Clin Med 10(4):607 Ronco P, Plaisier E, Debiec H (2021) Advances in membranous nephropathy. J Clin Med 10(4):607
90.
go back to reference Cattran DC, Brenchley PE (2017) Membranous nephropathy: integrating basic science into improved clinical management. Kidney Int 91(3):566–574PubMedCrossRef Cattran DC, Brenchley PE (2017) Membranous nephropathy: integrating basic science into improved clinical management. Kidney Int 91(3):566–574PubMedCrossRef
91.
go back to reference Qi Y-Y, Zhou X-J, Cheng F-J, Hou P, Ren Y-L, Wang S-X et al (2018) Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-α in lupus nephritis. Ann Rheum Dis 77(12):1799–1809PubMedCrossRef Qi Y-Y, Zhou X-J, Cheng F-J, Hou P, Ren Y-L, Wang S-X et al (2018) Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-α in lupus nephritis. Ann Rheum Dis 77(12):1799–1809PubMedCrossRef
Metadata
Title
New insights into the immune functions of podocytes: the role of complement
Authors
Valentina Bruno
Anne Katrin Mühlig
Jun Oh
Christoph Licht
Publication date
01-12-2023
Publisher
Springer International Publishing
Published in
Molecular and Cellular Pediatrics / Issue 1/2023
Electronic ISSN: 2194-7791
DOI
https://doi.org/10.1186/s40348-023-00157-3

Other articles of this Issue 1/2023

Molecular and Cellular Pediatrics 1/2023 Go to the issue