Advances of the experimental models of idiopathic membranous nephropathy (Review)

Jiang,Han   Xue; Feng,Zhendong; Zhu,Ze   Bing; Xia,Chen   Hui; Zhang,Wenting; Guo,Jing; Liu,Bao‑Li; Wang,Yaoxian; Liu,Yu   Ning; Liu,Wei  Jing

doi:10.3892/mmr.2020.11014

Advances of the experimental models of idiopathic membranous nephropathy (Review)

Authors:
- Han Xue Jiang
- Zhendong Feng
- Ze Bing Zhu
- Chen Hui Xia
- Wenting Zhang
- Jing Guo
- Bao‑Li Liu
- Yaoxian Wang
- Yu Ning Liu
- Wei Jing Liu
View Affiliations

Affiliations: Key Laboratory of Chinese Internal Medicine of The Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, P.R. China, Beijing Chinese Medicine Hospital Pinggu Hospital, Beijing 101200, P.R. China, Department of Nephrology, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing 100010, P.R. China
Published online on: March 9, 2020 https://doi.org/10.3892/mmr.2020.11014
Pages: 1993-2005
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Idiopathic membranous nephropathy (IMN) is one of the main types of chronic kidney disease in adults and one of the most common causes of end‑stage renal disease. In recent years, the morbidity of IMN among primary glomerular diseases has markedly increased, while the pathogenesis of the disease remains unclear. To address this, a number of experimental models, including Heymann nephritis, anti‑thrombospondin type‑1 domain‑containing 7A antibody‑induced IMN, cationic bovine serum albumin, anti‑human podocyte antibodies and zymosan‑activated serum‑induced C5b‑9, have been established. This review comprehensively summarized the available animal and cell models for IMN. The limitations and advantages of the current models were discussed and two improved models were introduced to facilitate the selection of an appropriate model for further studies on IMN.

View Figures

View References

1	Cernaro V, Coppolino G, Visconti L, Rivoli L, Lacquaniti A, Santoro D, Buemi A, Loddo S and Buemi M: Erythropoiesis and chronic kidney disease-related anemia: From physiology to new therapeutic advancements. Med Res Rev. 39:427–460. 2019. View Article : Google Scholar : PubMed/NCBI
2	Chen DQ, Cao G, Chen H, Argyopoulos CP, Yu H, Su W, Chen L, Samuels DC, Zhuang S, Bayliss GP, et al: Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan. Nat Commun. 10:14762019. View Article : Google Scholar : PubMed/NCBI
3	Chen DQ, Cao G, Zhao H, Chen L, Yang T, Wang M, Vaziri ND, Guo Y and Zhao YY: Combined melatonin and poricoic acid A inhibits renal fibrosis through modulating the interaction of Smad3 and β-catenin pathway in AKI-to-CKD continuum. Ther Adv Chronic Dis. 10:20406223198691162019. View Article : Google Scholar : PubMed/NCBI
4	MacKinnon HJ, Wilkinson TJ, Clarke AL, Gould DW, O'Sullivan TF, Xenophontos S, Watson EL, Singh SJ and Smith AC: The association of physical function and physical activity with all-cause mortality and adverse clinical outcomes in nondialysis chronic kidney disease: A systematic review. Ther Adv Chronic Dis. 9:209–226. 2018. View Article : Google Scholar : PubMed/NCBI
5	Xiaofan H, Jing X, Chenni G, Yifan W, Xialian Y, Li L, Hong R, Wen Z, Weiming W, Xiaoxia P, et al: New risk score for predicting progression of membranous nephropathy. J Transl Med. 17:412019. View Article : Google Scholar : PubMed/NCBI
6	Petrosyan A, Cravedi P, Villani V, Angeletti A, Manrique J, Renieri A, De Filippo RE, Perin L and Da Sacco S: A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier. Nat Commun. 10:36562019. View Article : Google Scholar : PubMed/NCBI
7	Glassock RJ: The pathogenesis of idiopathic membranous nephropathy: A 50-year odyssey. Am J Kidney Dis. 56:157–167. 2010. View Article : Google Scholar : PubMed/NCBI
8	Xu X, Wang G, Chen N, Lu T, Nie S, Xu G, Zhang P, Luo Y, Wang Y, Wang X, et al: Long-term exposure to air pollution and increased risk of membranous nephropathy in China. J Am Soc Nephrol. 27:3739–3746. 2016. View Article : Google Scholar : PubMed/NCBI
9	Zhu P, Zhou FD, Wang SX, Zhao MH and Wang HY: Increasing frequency of idiopathic membranous nephropathy in primary glomerular disease: A 10-year renal biopsy study from a single Chinese nephrology centre. Nephrology (Carlton). 20:560–566. 2015. View Article : Google Scholar : PubMed/NCBI
10	Pan X, Xu J, Ren H, Zhang W, Xu Y, Shen P, Li X, Wang W, Chen X, Wu P, et al: Changing spectrum of biopsy-proven primary glomerular diseases over the past 15 years: A single-center study in China. Contrib Nephrol. 181:22–30. 2013. View Article : Google Scholar : PubMed/NCBI
11	Chen X, Chen Y, Shi K, Lv Y, Tong H, Zhao G, Chen C, Chen B, Li D and Lu Z: Comparison of prognostic, clinical, and renal histopathological characteristics of overlapping idiopathic membranous nephropathy and IgA nephropathy versus idiopathic membranous nephropathy. Sci Rep. 7:114682017. View Article : Google Scholar : PubMed/NCBI
12	Maisonneuve P, Agodoa L, Gellert R, Stewart JH, Buccianti G, Lowenfels AB, Wolfe RA, Jones E, Disney AP, Briggs D, et al: Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: Results from an international comparative study. Am J Kidney Dis. 35:157–165. 2000. View Article : Google Scholar : PubMed/NCBI
13	Latt KZ, Honda K, Thiri M, Hitomi Y, Omae Y, Sawai H, Kawai Y, Teraguchi S, Ueno K, Nagasaki M, et al: Identification of a two-SNP PLA2R1 Haplotype and HLA-DRB1 Alleles as primary risk associations in idiopathic membranous nephropathy. Sci Rep. 8:155762018. View Article : Google Scholar : PubMed/NCBI
14	Couser WG: Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 12:983–997. 2017. View Article : Google Scholar : PubMed/NCBI
15	Troyanov S, Wall CA, Scholey JW, Miller JA and Cattran DC: Idiopathic membranous nephropathy: Definition and relevance of a partial remission. Kidney International. 66:1199–1205. 2004. View Article : Google Scholar : PubMed/NCBI
16	Cattran D and Brenchley P: Membranous nephropathy: Thinking through the therapeutic options. Nephrol Dial Transplant. 32:i22–i29. 2017. View Article : Google Scholar : PubMed/NCBI
17	Fontecha-Barriuso M, Martin-Sanchez D, Ruiz-Andres O, Poveda J, Sanchez-Niño MD, Valiño-Rivas L, Ruiz-Ortega M, Ortiz A and Sanz AB: Targeting epigenetic DNA and histone modifications to treat kidney disease. Nephrol Dial Transplant. 33:1875–1886. 2018. View Article : Google Scholar : PubMed/NCBI
18	Jefferson JA, Pippin JW and Shankland SJ: Experimental models of membranous nephropathy. Drug Discov Today Dis Models. 7:27–33. 2010. View Article : Google Scholar : PubMed/NCBI
19	Borza DB, Zhang JJ, Beck LH Jr, Meyer-Schwesinger C and Luo W: Mouse models of membranous nephropathy: The road less travelled by. Am J Clin Exp Immunol. 2:135–145. 2013.PubMed/NCBI
20	Tomas NM, Hoxha E, Reinicke AT, Fester L, Helmchen U, Gerth J, Bachmann F, Budde K, Koch-Nolte F, Zahner G, et al: Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy. J Clin Invest. 126:2519–2532. 2016. View Article : Google Scholar : PubMed/NCBI
21	Lim WH, Wong G, McDonald SP, Chakera A, Luxton G, Isbel NM, Pilmore HL, Barbour T, Hughes P and Chadban SJ: Long-term outcomes of kidney transplant recipients with end-stage kidney disease attributed to presumed/advanced glomerulonephritis or unknown cause. Sci Rep. 8:90212018. View Article : Google Scholar : PubMed/NCBI
22	Cybulsky AV, Quigg RJ and Salant DJ: Experimental membranous nephropathy redux. Am J Physiol Renal Physiol. 289:F660–F671. 2005. View Article : Google Scholar : PubMed/NCBI
23	Ma H, Sandor DG and Beck LH Jr: The role of complement in membranous nephropathy. Semin Nephrol. 33:531–542. 2013. View Article : Google Scholar : PubMed/NCBI
24	Heymann W, Hackel DB, Harwood S, Wilson SG and Hunter JL: Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions. Proc Soc Exp Biol Med. 100:660–664. 1959. View Article : Google Scholar : PubMed/NCBI
25	Salant DJ, Quigg RJ and Cybulsky AV: Heymann nephritis: Mechanisms of renal injury. Kidney Int. 35:976–984. 1989. View Article : Google Scholar : PubMed/NCBI
26	Christiansen RE, Kolmannskog O, Leh S, Iversen BM and Tenstad O: Glomerular charge barrier and development of proteinuria in passive Heymann nephritis. Kidney Blood Press Res. 31:203–209. 2008. View Article : Google Scholar : PubMed/NCBI
27	Salant DJ and Cybulsky AV: Experimental glomerulonephritis. Methods Enzymol. 162:421–461. 1988. View Article : Google Scholar : PubMed/NCBI
28	Kerjaschki D and Farquhar MG: The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci USA. 79:5557–5561. 1982. View Article : Google Scholar : PubMed/NCBI
29	Kerjaschki D and Farquhar MG: Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats. J Exp Med. 157:667–686. 1983. View Article : Google Scholar : PubMed/NCBI
30	Kerjaschki D, Ullrich R, Diem K, Pietromonaco S, Orlando RA and Farquhar MG: Identification of a pathogenic epitope involved in initiation of Heymann nephritis. Proc Natl Acad Sci USA. 89:11179–11183. 1992. View Article : Google Scholar : PubMed/NCBI
31	Raychowdhury R, Zheng G, Brown D and McCluskey RT: Induction of Heymann nephritis with a gp330/megalin fusion protein. Am J Pathol. 148:1613–1623. 1996.PubMed/NCBI
32	Couser WG: Mediation of immune glomerular injury. J Am Soc Nephrol. 1:13–29. 1990.PubMed/NCBI
33	Baker PJ, Ochi RF, Schulze M, Johnson RJ, Campbell C and Couser WG: Depletion of C6 prevents development of proteinuria in experimental membranous nephropathy in rats. Am J Pathol. 135:185–194. 1989.PubMed/NCBI
34	Prabakaran T, Nielsen R, Larsen JV, Sørensen SS, Feldt-Rasmussen U, Saleem MA, Petersen CM, Verroust PJ and Christensen EI: Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease. PLoS One. 6:e250652011. View Article : Google Scholar : PubMed/NCBI
35	Larsen C, Etzerodt A, Madsen M, Skjodt K, Moestrup SK and Andersen CBF: Structural assembly of the megadalton-sized receptor for intestinal vitamin B₁₂ uptake and kidney protein reabsorption. Nat Commun. 9:52042018. View Article : Google Scholar : PubMed/NCBI
36	Ronco P and Debiec H: Pathophysiological advances in membranous nephropathy: Time for a shift in patient's care. Lancet. 385:1983–1992. 2015. View Article : Google Scholar : PubMed/NCBI
37	Vinaiphat A and Thongboonkerd V: Characterizations of PMCA2-interacting complex and its role as a calcium oxalate crystal-binding protein. Cell Mol Life Sci. 75:1461–1482. 2018. View Article : Google Scholar : PubMed/NCBI
38	Beausang JF, Fan HC, Sit R, Hutchins MU, Jirage K, Curtis R, Hutchins E, Quake SR and Yabu JM: B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy. J Transl Med. 15:92017. View Article : Google Scholar : PubMed/NCBI
39	Rudkin FM, Raziunaite I, Workman H, Essono S, Belmonte R, MacCallum DM, Johnson EM, Silva LM, Palma AS, Feizi T, et al: Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis. Nat Commun. 9:52882018. View Article : Google Scholar : PubMed/NCBI
40	Natori Y, Shindo N and Natori Y: Proteinuria induced by anti-dipeptidyl peptidase IV (gp108); role of circulating and glomerular antigen. Clin Exp Immunol. 95:327–332. 1994. View Article : Google Scholar : PubMed/NCBI
41	Hunter JL, Hackel DB and Heymann W: Nephrotic syndrome in rats produced by sensitization to rat kidney proteins: Immunologic studies. J Immunol. 85:319–327. 1960.PubMed/NCBI
42	Tomas NM, Beck LH Jr, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, Dolla G, Hoxha E, Helmchen U, Dabert-Gay AS, et al: Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 371:2277–2287. 2014. View Article : Google Scholar : PubMed/NCBI
43	Glassock RJ: Pathogenesis of membranous nephropathy: A new paradigm in evolution. Contrib Nephrol. 181:131–142. 2013. View Article : Google Scholar : PubMed/NCBI
44	Tan K, Duquette M, Liu JH, Dong Y, Zhang R, Joachimiak A, Lawler J and Wang JH: Crystal structure of the TSP-1 type 1 repeats: A novel layered fold and its biological implication. J Cell Biol. 159:373–382. 2002. View Article : Google Scholar : PubMed/NCBI
45	Allison SJ: Glomerular disease: Thrombospondin type-1 domain-containing 7A-a new player in membranous nephropathy. Nat Rev Nephrol. 11:632015. View Article : Google Scholar : PubMed/NCBI
46	De Vriese AS, Glassock RJ, Nath KA, Sethi S and Fervenza FC: A Proposal for a serology-based approach to membranous nephropathy. J Am Soc Nephrol. 28:421–430. 2017. View Article : Google Scholar : PubMed/NCBI
47	Godel M, Grahammer F and Huber TB: Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 372:10732015. View Article : Google Scholar : PubMed/NCBI
48	Tomas NM, Meyer-Schwesinger C, von Spiegel H, Kotb AM, Zahner G, Hoxha E, Helmchen U, Endlich N, Koch-Nolte F and Stahl RAK: A Heterologous model of thrombospondin type 1 domain-containing 7A-associated membranous nephropathy. J Am Soc Nephrol. 28:3262–3277. 2017. View Article : Google Scholar : PubMed/NCBI
49	Assmann KJ, van Son JP, Dijkman HB and Koene RA: A nephritogenic rat monoclonal antibody to mouse aminopeptidase A. Induction of massive albuminuria after a single intravenous injection. J Exp Med. 175:623–635. 1992. View Article : Google Scholar : PubMed/NCBI
50	Dijkman HB, Gerlofs-Nijland ME, van der Laak JA, Wetzels JF, Groenen PJ and Assmann KJ: Podocyte changes after induction of acute albuminuria in mice by anti-aminopeptidase A mAb. Nephron Exp Nephrol. 94:e85–e93. 2003. View Article : Google Scholar : PubMed/NCBI
51	Border WA, Ward HJ, Kamil ES and Cohen AH: Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen. J Clin Invest. 69:451–461. 1982. View Article : Google Scholar : PubMed/NCBI
52	Liu B, Lu R, Li H, Zhou Y, Zhang P, Bai L, Chen D, Chen J, Li J, Yu P, et al: Zhen-wu-tang ameliorates membranous nephropathy rats through inhibiting NF-κB pathway and NLRP3 inflammasome. Phytomedicine. 59:1529132019. View Article : Google Scholar : PubMed/NCBI
53	Adler SG, Wang H, Ward HJ, Cohen AH and Border WA: Electrical charge. Its role in the pathogenesis and prevention of experimental membranous nephropathy in the rabbit. J Clin Invest. 71:487–499. 1983. View Article : Google Scholar : PubMed/NCBI
54	Chen JS, Chen A, Chang LC, Chang WS, Lee HS, Lin SH and Lin YF: Mouse model of membranous nephropathy induced by cationic bovine serum albumin: Antigen dose-response relations and strain differences. Nephrol Dial Transplant. 19:2721–2728. 2004. View Article : Google Scholar : PubMed/NCBI
55	Debiec H, Lefeu F, Kemper MJ, Niaudet P, Deschênes G, Remuzzi G, Ulinski T and Ronco P: Early-childhood membranous nephropathy due to cationic bovine serum albumin. N Engl J Med. 364:2101–2110. 2011. View Article : Google Scholar : PubMed/NCBI
56	Zhang JJ, Malekpour M, Luo W, Ge L, Olaru F, Wang XP, Bah M, Sado Y, Heidet L, Kleinau S, et al: Murine membranous nephropathy: Immunization with α3(IV) collagen fragment induces subepithelial immune complexes and FcγR-independent nephrotic syndrome. J Immunol. 188:3268–3277. 2012. View Article : Google Scholar : PubMed/NCBI
57	Hopfer H, Hunemorder S, Treder J, Turner JE, Paust HJ, Meyer-Schwesinger C, Hopfer U, Sachs M, Peters A, Bucher-Kocaoglu B, et al: Glomerulopathy induced by immunization with a peptide derived from the goodpasture antigen α3IV-NC1. J Immunol. 194:3646–3655. 2015. View Article : Google Scholar : PubMed/NCBI
58	Luo W, Olaru F, Miner JH, Beck LH Jr, van der Vlag J, Thurman JM and Borza DB: Alternative pathway is essential for glomerular complement activation and proteinuria in a mouse model of membranous nephropathy. Front Immunol. 9:14332018. View Article : Google Scholar : PubMed/NCBI
59	Hopfer H, Maron R, Butzmann U, Helmchen U, Weiner HL and Kalluri R: The importance of cell-mediated immunity in the course and severity of autoimmune anti-glomerular basement membrane disease in mice. FASEB J. 17:860–868. 2003. View Article : Google Scholar : PubMed/NCBI
60	Meyer TN, Schwesinger C, Wahlefeld J, Dehde S, Kerjaschki D, Becker JU, Stahl RA and Thaiss F: A new mouse model of immune-mediated podocyte injury. Kidney Int. 72:841–852. 2007. View Article : Google Scholar : PubMed/NCBI
61	Tsai SF, Wu MJ and Chen CH: Low serum C3 level, high neutrophil-lymphocyte-ratio, and high platelet-lymphocyte-ratio all predicted poor long-term renal survivals in biopsy-confirmed idiopathic membranous nephropathy. Scie Rep. 9:62092019. View Article : Google Scholar
62	Meyer-Schwesinger C, Dehde S, Klug P, Becker JU, Mathey S, Arefi K, Balabanov S, Venz S, Endlich KH, Pekna M, et al: Nephrotic syndrome and subepithelial deposits in a mouse model of immune-mediated anti-podocyte glomerulonephritis. J Immunol. 187:3218–3229. 2011. View Article : Google Scholar : PubMed/NCBI
63	Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB and Salant DJ: M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 361:11–21. 2009. View Article : Google Scholar : PubMed/NCBI
64	Debiec H and Ronco P: Immune response against autoantigen PLA2R is not gambling: Implications for pathophysiology, prognosis, and therapy. J Am Soc Nephrol. 27:1275–1277. 2016. View Article : Google Scholar : PubMed/NCBI
65	Pandey P, Roy KK, Liu H, Ma G, Pettaway S, Alsharif WF, Gadepalli RS, Rimoldi JM, McCurdy CR, Cutler SJ and Doerksen RJ: Structure-based identification of potent natural product chemotypes as cannabinoid receptor 1 inverse agonists. Molecules. 23(pii): E26302018. View Article : Google Scholar : PubMed/NCBI
66	Wang J, Cui Z, Lu J, Probst C, Zhang YM, Wang X, Qu Z, Wang F, Meng LQ, Cheng XY, et al: Circulating antibodies against thrombospondin type-I domain-containing 7A in Chinese patients with idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 12:1642–1651. 2017. View Article : Google Scholar : PubMed/NCBI
67	Liu W, Gao C, Dai H, Zheng Y, Dong Z, Gao Y, Liu F, Zhang Z, Liu Z, Liu W, et al: Immunological pathogenesis of membranous nephropathy: Focus on PLA2R1 and Its role. Front Immunol. 10:18092019. View Article : Google Scholar : PubMed/NCBI
68	Song JS, Kim YJ, Han KU, Yoon BD and Kim JW: Zymosan and PMA activate the immune responses of Mutz3-derived dendritic cells synergistically. Immunol Lett. 167:41–46. 2015. View Article : Google Scholar : PubMed/NCBI
69	Gawryl MS, Simon MT, Eatman JL and Lint TF: An enzyme-linked immunoabsorbent assay for the quantitation of the terminal complement complex from cell membranes or in activated human sera. J Immunol Methods. 95:217–225. 1986. View Article : Google Scholar : PubMed/NCBI
70	Ishikawa S, Tsukada H and Bhattacharya J: Soluble complex of complement increases hydraulic conductivity in single microvessels of rat lung. J Clin Invest. 91:103–109. 1993. View Article : Google Scholar : PubMed/NCBI
71	Liu WJ, Li ZH, Chen XC, Zhao XL, Zhong Z, Yang C, Wu HL, An N, Li WY and Liu HF: Blockage of the lysosome-dependent autophagic pathway contributes to complement membrane attack complex-induced podocyte injury in idiopathic membranous nephropathy. Sci Rep. 7:86432017. View Article : Google Scholar : PubMed/NCBI
72	Fearon DT and Austen KF: Activation of the alternative complement pathway due to resistance of zymosan-bound amplification convertase to endogenous regulatory mechanisms. Proc Natl Acad Sci USA. 74:1683–1687. 1977. View Article : Google Scholar : PubMed/NCBI
73	Tegla CA, Cudrici C, Patel S, Trippe R III, Rus V, Niculescu F and Rus H: Membrane attack by complement: The assembly and biology of terminal complement complexes. Immunol Res. 51:45–60. 2011. View Article : Google Scholar : PubMed/NCBI
74	Harboe M, Garred P, Lindstad JK, Pharo A, Müller F, Stahl GL, Lambris JD and Mollnes TE: The role of properdin in zymosan- and Escherichia coli-induced complement activation. J Immunol. 189:2606–2613. 2012. View Article : Google Scholar : PubMed/NCBI
75	Rawal N and Pangburn MK: C5 convertase of the alternative pathway of complement. Kinetic analysis of the free and surface-bound forms of the enzyme. J Biol Chem. 273:16828–16835. 1998. View Article : Google Scholar : PubMed/NCBI
76	Rawal N and Pangburn M: Formation of high-affinity C5 convertases of the alternative pathway of complement. J Immunol. 166:2635–2642. 2001. View Article : Google Scholar : PubMed/NCBI
77	Zhang MH, Fan JM, Xie XS, Deng YY, Chen YP, Zhen R, Li J, Cheng Y and Wen J: Ginsenoside-Rg1 protects podocytes from complement mediated injury. J Ethnopharmacol. 137:99–107. 2011. View Article : Google Scholar : PubMed/NCBI
78	Zhang C, Leng L, Zhang X, Zhao Y and Li Z: Comprehensive identification of immune-associated biomarkers based on network and mRNA expression patterns in membranous glomerulonephritis. J Transl Med. 16:2102018. View Article : Google Scholar : PubMed/NCBI
79	Bruschi M, Petretto A, Santucci L, Vaglio A, Pratesi F, Migliorini P, Bertelli R, Lavarello C, Bartolucci M, Candiano G, et al: Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized alphaenolase (methionine sulfoxide 93). Scie Rep. 9:79342019. View Article : Google Scholar
80	Li LZ, Hu Y, Ai SL, Cheng L, Liu J, Morris E, Li Y, Gou SJ and Fu P: The relationship between thyroid dysfunction and nephrotic syndrome: A clinicopathological study. Sci Rep. 9:64212019. View Article : Google Scholar : PubMed/NCBI
81	Pozdzik A, Brocheriou I, David C, Touzani F, Goujon JM and Wissing KM: Membranous nephropathy and anti-podocytes antibodies: Implications for the diagnostic workup and disease management. Biomed Res Int. 2018:62810542018. View Article : Google Scholar : PubMed/NCBI
82	Borsos T: Immune complex mediated activation of the classic complement pathway. Behring Inst Mitt. 93–101. 1989.PubMed/NCBI
83	Cattran DC and Brenchley PE: Membranous nephropathy: Integrating basic science into improved clinical management. Kidney Int. 91:566–574. 2017. View Article : Google Scholar : PubMed/NCBI
84	Zhang Q, Huang B, Liu X, Liu B, Zhang Y, Zhang Z, Hua J, Fan Y, Hu L, Meng M, et al: Ultrasensitive quantitation of anti-phospholipase A2 receptor antibody as a diagnostic and prognostic indicator of idiopathic membranous nephropathy. Sci Rep. 7:120492017. View Article : Google Scholar : PubMed/NCBI
85	Fresquet M, Jowitt TA, McKenzie EA, Ball MD, Randles MJ, Lennon R and Brenchley PE: PLA₂R binds to the annexin A2-S100A10 complex in human podocytes. Sci Rep. 7:68762017. View Article : Google Scholar : PubMed/NCBI
86	Vidarsson G, Dekkers G and Rispens T: IgG subclasses and allotypes: From structure to effector functions. Front Immunol. 5:5202014. View Article : Google Scholar : PubMed/NCBI
87	Borza DB: Alternative pathway dysregulation and the conundrum of complement activation by IgG4 immune complexes in membranous nephropathy. Front Immunol. 7:1572016. View Article : Google Scholar : PubMed/NCBI
88	Wang Z, Wen L, Dou Y and Zhao Z: Human anti-thrombospondin type 1 domain-containing 7A antibodies induce membranous nephropathy through activation of lectin complement pathway. Biosci Rep. 38(pii): BSR201801312018. View Article : Google Scholar : PubMed/NCBI
89	Hayashi N, Okada K, Matsui Y, Fujimoto K, Adachi H, Yamaya H, Matsushita M and Yokoyama H: Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy. Nephrol Dial Transplant. 33:832–840. 2018. View Article : Google Scholar : PubMed/NCBI
90	Garred P, Genster N, Pilely K, Bayarri-Olmos R, Rosbjerg A, Ma YJ and Skjoedt MO: A journey through the lectin pathway of complement-MBL and beyond. Immunol Rev. 274:74–97. 2016. View Article : Google Scholar : PubMed/NCBI
91	Bally S, Debiec H, Ponard D, Dijoud F, Rendu J, Fauré J, Ronco P and Dumestre-Perard C: Phospholipase A2 Receptor-related membranous nephropathy and mannan-binding lectin deficiency. J Am Soc Nephrol. 27:3539–3544. 2016. View Article : Google Scholar : PubMed/NCBI
92	Hoxha E, Wiech T, Stahl PR, Zahner G, Tomas NM, Meyer-Schwesinger C, Wenzel U, Janneck M, Steinmetz OM, Panzer U, et al: A mechanism for Cancer-associated membranous nephropathy. N Engl J Med. 374:1995–1996. 2016. View Article : Google Scholar : PubMed/NCBI
93	Matsumoto A, Matsui I, Namba T, Sakaguchi Y, Mizuno H, Shirayama Y, Shimada K, Hashimoto N, Doi Y, Yamaguchi S, et al: VEGF-A links angiolymphoid hyperplasia with eosinophilia (ALHE) to THSD7A membranous nephropathy: A report of 2 cases. Am J Kidney Dis. 73:880–885. 2019. View Article : Google Scholar : PubMed/NCBI
94	Xu X, Wang G, Chen N, Lu T, Nie S, Xu G, Zhang P, Luo Y, Wang Y, Wang X, et al: Long-term exposure to air pollution and increased risk of membranous nephropathy in China. J Am Soc Nephrol. 27:3739–3746. 2016. View Article : Google Scholar : PubMed/NCBI
95	Silliman CC, Moore EE, Zallen G, Gonzalez R, Johnson JL, Elzi DJ, Meng X, Hanasaki K, Ishizaki J, Arita H, et al: Presence of the M-type sPLA(2) receptor on neutrophils and its role in elastase release and adhesion. Am J Physiol Cell Physiol. 283:C1102–C1113. 2002. View Article : Google Scholar : PubMed/NCBI
96	Granata F, Petraroli A, Boilard E, Bezzine S, Bollinger J, Del Vecchio L, Gelb MH, Lambeau G, Marone G and Triggiani M: Activation of cytokine production by secreted phospholipase A2 in human lung macrophages expressing the M-type receptor. J Immunol. 174:464–474. 2005. View Article : Google Scholar : PubMed/NCBI
97	Beck LH Jr: PLA2R and THSD7A: Disparate paths to the same disease? J Am Soc Nephrol. 28:2579–2589. 2017. View Article : Google Scholar : PubMed/NCBI
98	Chiorazzo MG, Tunset HM, Popov AV, Johansen B, Moestue S and Delikatny EJ: Detection and differentiation of breast cancer Sub-types using a cPLA2α activatable fluorophore. Sci Rep. 9:61222019. View Article : Google Scholar : PubMed/NCBI
99	Pan Q, Lan Q, Peng Y, Cai J, Zheng J, Dickerson C, Xiao H and Liu HF: Nature, functions, and clinical implications of IgG4 autoantibodies in systemic lupus erythematosus and rheumatoid arthritis. Discov Med. 23:169–174. 2017.PubMed/NCBI
100	Salant DJ: Unmet challenges in membranous nephropathy. Curr Opin Nephrol Hypertens. 28:70–76. 2019. View Article : Google Scholar : PubMed/NCBI
101	Borza DB: Alternative pathway dysregulation and the conundrum of complement activation by IgG4 immune complexes in membranous nephropathy. Front Immunol. 7:1572016. View Article : Google Scholar : PubMed/NCBI
102	Liu D, Zhang J, Shi Y and Liu Z: Gene polymorphism and risk of idiopathic membranous nephropathy. Life Sci. 229:124–131. 2019. View Article : Google Scholar : PubMed/NCBI
103	Canadas-Garre M, Anderson K, McGoldrick J, Maxwell AP and McKnight AJ: Genomic approaches in the search for molecular biomarkers in chronic kidney disease. J Transl Med. 16:2922018. View Article : Google Scholar : PubMed/NCBI
104	Kamyshova ES, Bobkova IN, Gorelova IA, Каkhsurueva PA and Filatova EE: Genetic determinants of the development and course of membranous nephropathy. Ter Arkh. 90:105–111. 2018.PubMed/NCBI
105	Lan HY, Mu W, Tomita N, Huang XR, Li JH, Zhu HJ, Morishita R and Johnson RJ: Inhibition of renal fibrosis by gene transfer of inducible Smad7 using ultrasound-microbubble system in rat UUO model. J Am Soc Nephrol. 14:1535–1548. 2003. View Article : Google Scholar : PubMed/NCBI
106	Fujii H, Li SH, Wu J, Miyagi Y, Yau TM, Rakowski H, Egashira K, Guo J, Weisel RD and Li RK: Repeated and targeted transfer of angiogenic plasmids into the infarcted rat heart via ultrasound targeted microbubble destruction enhances cardiac repair. Eur Heart J. 32:2075–2084. 2011. View Article : Google Scholar : PubMed/NCBI
107	Huang B, Wang L, Zhang Y, Zhang J, Zhang Q, Xiao H, Zhou B, Sun Z, Cao YN, Chen Y, et al: A novel Time-resolved Fluoroimmunoassay for the quantitative detection of Antibodies against the phospholipase A2 receptor. Sci Rep. 7:460962017. View Article : Google Scholar : PubMed/NCBI
108	Pan Y, Wan J, Liu Y, Yang Q, Liang W, Singhal PC, Saleem MA and Ding G: sPLA2 IB induces human podocyte apoptosis via the M-type phospholipase A2 receptor. Sci Re. 4:66602014.
109	Lambeau G and Lazdunski M: Receptors for a growing family of secreted phospholipases A2. Trends Pharmacol Sci. 20:162–170. 1999. View Article : Google Scholar : PubMed/NCBI
110	Tamaru S, Mishina H, Watanabe Y, Watanabe K, Fujioka D, Takahashi S, Suzuki K, Nakamura T, Obata JE, Kawabata K, et al: Deficiency of phospholipase A2 receptor exacerbates ovalbumin-induced lung inflammation. J Immunol. 191:1021–1028. 2013. View Article : Google Scholar : PubMed/NCBI
111	Chen DQ, Feng YL, Cao G and Zhao YY: Natural products as a source for antifibrosis therapy. Trends Pharmacol Sci. 39:937–952. 2018. View Article : Google Scholar : PubMed/NCBI
112	Chen DQ, Hu HH, Wang YN, Feng YL, Cao G and Zhao YY: Natural products for the prevention and treatment of kidney disease. Phytomedicine. 50:50–60. 2018. View Article : Google Scholar : PubMed/NCBI
113	Wang M, Chen DQ, Chen L, Cao G, Zhao H, Liu D, Vaziri ND, Guo Y and Zhao YY: Novel inhibitors of the cellular renin-angiotensin system components, poricoic acids, target Smad3 phosphorylation and Wnt/beta-catenin pathway against renal fibrosis. Br J Pharmacol. 175:2689–2708. 2018. View Article : Google Scholar : PubMed/NCBI
114	Chen Y, Deng Y, Ni Z, Chen N, Chen X, Shi W, Zhan Y, Yuan F, Deng W and Zhong Y: Efficacy and safety of traditional Chinese medicine (Shenqi Particle) for patients with idiopathic membranous nephropathy: A multicenter randomized controlled clinical trial. Am J Kidney Dis. 62:1068–1076. 2013. View Article : Google Scholar : PubMed/NCBI
115	Zhang L, Li P, Xing CY, Zhao JY, He YN, Wang JQ, Wu XF, Liu ZS, Zhang AP, Lin HL, et al: Efficacy and safety of Abelmoschus manihot for primary glomerular disease: A prospective, multicenter randomized controlled clinical trial. Am J Kidney Dis. 64:57–65. 2014. View Article : Google Scholar : PubMed/NCBI
116	Liu S, Li X, Li H, Liang Q and Chen J and Chen J: Comparison of tripterygium wilfordii multiglycosides and tacrolimus in the treatment of idiopathic membranous nephropathy: A prospective cohort study. BMC Nephrol. 16:2002015. View Article : Google Scholar : PubMed/NCBI