Animal models of membranous nephropathy: more choices and higher similarity

Front Immunol. 2024 Oct 21:15:1412826. doi: 10.3389/fimmu.2024.1412826. eCollection 2024.

Abstract

Membranous nephropathy (MN) is an antibody-mediated autoimmune glomerular disease in which PLA2R1 is the main autoantibody. It has become the most common cause of adult nephrotic syndrome, and about one-third of patients can progress to end-stage kidney disease, but its pathogenesis is still unclear. Animal models can be used as suitable tools to study the pathogenesis and treatment of MN. The previous Heymann nephritis rat model and C-BSA animal model are widely used to study the pathogenesis of MN. However, the lack of target antigen expression in podocytes of model animals (especially rodents) restricts the application. In recent years, researchers constructed animal models of antigen-specific MN, such as THSD7A, PLA2R1, which more truly simulate the pathogenesis and pathological features of MN and provide more choices for the follow-up researchers. When selecting these MN models, we need to consider many aspects, including cost, difficulty of model preparation, labor force, and whether the final model can answer the research questions. This review is to comprehensively evaluate the mechanism, advantages and disadvantages and feasibility of existing animal models, and provide new reference for the pathogenesis and treatment of MN.

Keywords: advantages; animal model; disadvantages; end stage kidney disease; membranous nephropathy.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Disease Models, Animal*
  • Glomerulonephritis, Membranous* / immunology
  • Glomerulonephritis, Membranous* / pathology
  • Humans
  • Podocytes / immunology
  • Podocytes / pathology
  • Rats
  • Receptors, Phospholipase A2* / immunology
  • Thrombospondins / immunology
  • Thrombospondins / metabolism

Substances

  • Receptors, Phospholipase A2
  • Autoantibodies
  • Thrombospondins
  • PLA2R1 protein, human
  • THSD7A protein, human

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China (82170699, 81870469 to YY), “PRO•Run” Fund of the Nephrology Group of CEBM (KYJ202206-0003-6 to YY), the “ 333 Project “ of Jiangsu Province, the Six Talent Peaks Project in Jiangsu Province (WSN-010 to YY), “Yiluqihang • Shenmingyuanyang” medical development and Scientific Research Fund project on Kidney Diseases (SMYY20220301001 to YY), and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institution.