The Role of Podocytes in Lupus Pathology

Tsokos GC. Mechanisms of Disease systemic lupus erythematosus. N Engl J Med. 2011;365:2110–31.

Article  CAS  PubMed  Google Scholar 

Tektonidou MG, Dasgupta A, Ward MM. Risk of end-stage renal disease in patients with Lupus Nephritis, 1971–2015: a systematic review and bayesian Meta-analysis. Arthritis Rheumatol. 2016;68:1432–41.

Article  PubMed  PubMed Central  Google Scholar 

Yu F, Haas M, Glassock R, Zhao MH. Redefining lupus nephritis: clinical implications of pathophysiologic subtypes. Nat Rev Nephrol Nat. 2017;13:483–95 (Publishing Group).

Hu W, Chen Y, Wang S, Chen H, Liu Z, Zeng C, et al. Clinical–morphological features and outcomes of lupus podocytopathy. Clin J Am Soc Nephrol. 2016;11:585–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tsokos GC. Autoimmunity and organ damage in systemic lupus erythematosus. Nat Immunol Nat Res. 2020;21:605–14.

Article  CAS  Google Scholar 

Tsokos GC, Boulougoura A, Kasinath V, Endo Y, Abdi R, Li H. The immunoregulatory roles of non-haematopoietic cells in the kidney. Nat Rev Nephrol Nat Res; 2024;20:206–17.

Article  CAS  Google Scholar 

Perico L, Conti S, Benigni A, Remuzzi G. Podocyte-actin dynamics in health and disease. Nat Rev Nephrol. 2016;12:692–710 (Nature Publishing Group).

Watts AJB, Keller KH, Lerner G, Rosales I, Collins AB, Sekulic M, et al. Discovery of autoantibodies Targeting Nephrin in Minimal Change Disease supports a novel autoimmune etiology. J Am Soc Nephrol. 2022;33:238–52.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hengel FE, Dehde S, Lassé M, Zahner G, Seifert L, Schnarre A et al. Autoantibodies targeting nephrin in Podocytopathies. N Engl J Med. 2024;391(5):422-433.

Asanuma K, Kim K, Oh J, Giardino L, Chabanis S, Faul C, et al. Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner. J Clin Invest. 2005;115:1188–98.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sakhi H, Moktefi A, Bouachi K, Audard V, Hénique C, Remy P, et al. Podocyte injury in lupus nephritis. J Clin Med MDPI. 2019;8(9):1340.

Article  CAS  Google Scholar 

Rezende GM, Viana VS, Malheiros DMAC, Borba EF, Silva NAS, Silva C, et al. Podocyte injury in pure membranous and proliferative lupus nephritis: distinct underlying mechanisms of proteinuria? Lupus. 2014;23:255–62.

Article  CAS  PubMed  Google Scholar 

Dall’Era M, Cisternas MG, Smilek DE, Straub L, Houssiau FA, Cervera R, et al. Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the euro-lupus nephritis cohort. Arthritis Rheumatol. 2015;67:1305–13.

Article  PubMed  Google Scholar 

Nagata M. Podocyte injury and its consequences. Kidney Int. 2016;89:1221–30 (Elsevier B.V.).

Perez-Hernandez J, Olivares MD, Forner MJ, Chaves FJ, Cortes R, Redon J. Urinary dedifferentiated podocytes as a non-invasive biomarker of lupus nephritis. Nephrol Dial Transpl. 2016;31:780–9.

Article  CAS  Google Scholar 

Lasagni L, Lazzeri E, Shankland SJ, Anders HJ, Romagnani P. Podocyte mitosis - a catastrophe. Curr Mol Med. 13(1):13-23. https://doi.org/10.2174/1566524011307010013.

Tian X, Pedigo CE, Li K, Ma X, Bunda P, Pell J, et al. Profilin1 is required for prevention of mitotic catastrophe in murine and human glomerular diseases. J Clin Invest. 2023;133(24):e171237.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Asanuma K, Yanagida-Asanuma E, Faul C, Tomino Y, Kim K, Mundel P. Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling. Nat Cell Biol. 2006;8:485–91.

Article  CAS  PubMed  Google Scholar 

Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. 2008;14:931–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liao R, Liu Q, Zheng Z, Fan J, Peng W, Kong Q et al. Tacrolimus protects podocytes from injury in lupus nephritis partly by stabilizing the cytoskeleton and inhibiting podocyte apoptosis. PLoS ONE. 2015;10:e0132724.

Article  PubMed  PubMed Central  Google Scholar 

Maeda K, Otomo K, Yoshida N, Abu-Asab MS, Ichinose K, Nishino T, et al. CaMK4 compromises podocyte function in autoimmune and nonautoimmune kidney disease. J Clin Invest. 2018;128:3445–59.

Article  PubMed  PubMed Central  Google Scholar 

Bhargava R, Lehoux S, Maeda K, Tsokos MG, Krishfield S, Ellezian L, et al. Aberrantly glycosylated IgG elicits pathogenic signaling in podocytes and signifies lupus nephritis. JCI Insight. 2021;6(9):e147789. https://doi.org/10.1172/jci.insight.147789.

Article  PubMed  PubMed Central  Google Scholar 

Fu J, Wang Z, Lee K, Wei C, Liu Z, Zhang M, et al. Transcriptomic analysis uncovers novel synergistic mechanisms in combination therapy for lupus nephritis. Kidney Int. 2018;93:416–29.

Article  CAS  PubMed  Google Scholar 

Fu R, Wang W, Huo Y, Li L, Chen R, Lin Z et al. The mechanosensitive ion channel Piezo1 contributes to podocyte cytoskeleton remodeling and development of proteinuria in lupus nephritis. Kidney Int [Internet]. 2024;134(15):e176402. https://linkinghub.elsevier.com/retrieve/pii/S0085253824005295

Tsokos GC. The immunology of systemic lupus erythematosus. Nat. Immunol. 2024;25(8):1332-1343 (del Nature Research).

Devarapu SK, Anders HJ. Toll-like receptors in lupus nephritis. J Biomed Sci. 2018;25:1-11 (del BioMed Central Ltd.).

Kimura J, Ichii O, Miyazono K, Nakamura T, Horino T, Otsuka-Kanazawa S et al. Overexpression of toll-like receptor 8 correlates with the progression of podocyte injury in murine autoimmune glomerulonephritis. Sci Rep. 2014;4:7290.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leadbetter EA, Rifkin IR, Hohlbaum AM, Beaudette BC, Shlomchik MJ, Marshak-Rothstein A. Chromatin-IgG complexes activate B cells by dual engagement of IgM and toll-like receptors. 2002;416(6881):603–7. https://doi.org/10.1038/416603a.

Article  CAS  Google Scholar 

Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest. 2005;115:407–17.

Article  CAS  PubMed  PubMed Central  Google Scholar 

MacHida H, Ito S, Hirose T, Takeshita F, Oshiro H, Nakamura T, et al. Expression of toll-like receptor 9 in renal podocytes in childhood-onset active and inactive lupus nephritis. Nephrol Dial Transpl. 2010;25:2530–7.

Article  Google Scholar 

Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes. Cell. 2014;157:1013–22 (Elsevier B.V.).

Fu R, Guo C, Wang S, Huang Y, Jin O, Hu H, et al. Podocyte activation of NLRP3 inflammasomes contributes to the development of Proteinuria in Lupus Nephritis. Arthritis Rheumatol. 2017;69:1636–46.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cai M, Zhou T, Wang X, Shang M, Zhang Y, Luo M, et al. DC-SIGN expression on podocytes and its role in inflammatory immune response of lupus nephritis. Clin Exp Immunol. 2016;183:317–25.

Article  CAS  PubMed  Google Scholar 

Yamaguchi J, Isnard P, Robil N, de la Grange P, Hoguin C, Schmitt A, et al. PIK3CA inhibition in models of proliferative glomerulonephritis and lupus nephritis. J Clin Invest. 2024;134(15):e176402.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li S, Liu Y, He Y, Rong W, Zhang M, Li L, et al. Podocytes present antigen to activate specific T cell immune responses in inflammatory renal disease. J Pathol. 2020;252:165–77.

Article  CAS  PubMed  Google Scholar 

Zoja C, Wang JM, Bettoni S, Sironi M, Renzi D, Chiaffarino F, et al. Interleukin-1 3 and Tumor Necrosis factor-ot induce Gene expression and production of Leukocyte Chemotactic Factors, colony-stimulating factors, and Interleukin-6 in human mesangial cells from the Mario Negri Institute for Pharnacological. Am. J. OfPathology; 1991.

Google Scholar 

Zhang Z, Niu L, Tang X, Feng R, Yao G, Chen W, et al. Mesenchymal stem cells prevent podocyte injury in lupus-prone B6.MRL-Faslpr mice via polarizing macrophage into an anti-inflammatory phenotype. Nephrol Dial Transpl. 2019;34:597–605.

Article  CAS  Google Scholar 

Bruschi M, Moroni G, Sinico RA, Franceschini F, Fredi M, Vaglio A, et al. Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (part 2): prospective study. Rheumatol U K. 2021;60:3388–97.

Article  CAS  Google Scholar 

Ichinose K, Ushigusa T, Nishino A, Nakashima Y, Suzuki T, Horai Y, et al. Lupus Nephritis IgG induction of Calcium/Calmodulin-Dependent protein kinase IV expression in Podocytes and Alteration of their function. Arthritis Rheumatol. 2016;68:944–52.

Comments (0)

No login
gif