The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis

Hackl, A.; Nüsken, E.; Voggel, J.; Abo Zed, S. E. D.; Binz-Lotter, J.; Unnersjö-Jess, D.; Müller, C.; Fink, G.; Bohl, K.; Wiesner, E.; Diefenhardt, P.; Dafinger, C.; Chen, H.; Wohlfarth, M.; Müller, R.-U.; Hackl, M. J.; Schermer, B.; Nüsken, K.-D.; Weber, L. T.

doi:10.1038/s41598-023-41222-1

Cited by 3 publications

(1 citation statement)

References 40 publications

(48 reference statements)

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“…Nevertheless, several lines of research provide intriguing insights into potential modes of action. It has been suggested that one facet of MMF’s protective effect against podocyte injury could be attributed to its role in restoring the integrity of the cytoskeletal axis of actin filaments ( 169 , 170 ). Furthermore, experiments utilizing diabetic mouse models treated with MMF showed a notable reduction in the number of infiltrated CD4 and CD8 T cells within the kidneys.…”

Section: Therapeutic Strategies Targeting Immunity In Podocyte Injurymentioning

confidence: 99%

Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy

Jiang,

Shen,

Zhuang

et al. 2024

Front. Immunol.

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The glomerular filtration barrier, comprising the inner layer of capillary fenestrated endothelial cells, outermost podocytes, and the glomerular basement membrane between them, plays a pivotal role in kidney function. Podocytes, terminally differentiated epithelial cells, are challenging to regenerate once injured. They are essential for maintaining the integrity of the glomerular filtration barrier. Damage to podocytes, resulting from intrinsic or extrinsic factors, leads to proteinuria in the early stages and eventually progresses to chronic kidney disease (CKD). Immune-mediated podocyte injury is a primary pathogenic mechanism in proteinuric glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and lupus nephritis with podocyte involvement. An extensive body of evidence indicates that podocytes not only contribute significantly to the maintenance of the glomerular filtration barrier and serve as targets of immune responses but also exhibit immune cell-like characteristics, participating in both innate and adaptive immunity. They play a pivotal role in mediating glomerular injury and represent potential therapeutic targets for CKD. This review aims to systematically elucidate the mechanisms of podocyte immune injury in various podocyte lesions and provide an overview of recent advances in podocyte immunotherapy. It offers valuable insights for a deeper understanding of the role of podocytes in proteinuric glomerular diseases, and the identification of new therapeutic targets, and has significant implications for the future clinical diagnosis and treatment of podocyte-related disorders.

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Section: Therapeutic Strategies Targeting Immunity In Podocyte Injurymentioning

confidence: 99%

Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy

Jiang,

Shen,

Zhuang

et al. 2024

Front. Immunol.

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Correlative multiphoton-STED microscopy of podocyte calcium levels and slit diaphragm ultrastructure in the renal glomerulus

Wiesner,

Binz-Lotter,

Hackl

et al. 2024

Sci Rep

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In recent years functional multiphoton (MP) imaging of vital mouse tissues and stimulation emission depletion (STED) imaging of optically cleared tissues allowed new insights into kidney biology. Here, we present a novel workflow where MP imaging of calcium signals can be combined with super-resolved STED imaging for morphological analysis of the slit diaphragm (SD) within the same glomerulus. Mice expressing the calcium indicator GCaMP3 in podocytes served as healthy controls or were challenged with two different doses of nephrotoxic serum (NTS). NTS induced glomerular damage in a dose dependent manner measured by shortening of SD length. In acute kidney slices (AKS) intracellular calcium levels increased upon disease but showed a high variation between glomeruli. We could not find a clear correlation between intracellular calcium levels and SD length in the same glomerulus. Remarkably, analysis of the SD morphology of glomeruli selected during MP calcium imaging revealed a higher percentage of completely disrupted SD architecture than estimated by STED imaging alone. Our novel co-imaging protocol is applicable to a broad range of research questions. It can be used with different tissues and is compatible with diverse reporters and target proteins.

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Assessment of the Potential Impact of Mycophenolate Mofetil on Lowering Renal Biomarkers in Patients with Class III Lupus Nephritis: A Pilot Study to Predict Renal Function Progress

Mohammed,

Al-Taie,

Al-Sultany

2024

Biomedical and Biotechnology Research Journal

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Background: Lupus nephritis (LN) is a potentially severe complication of systemic lupus erythematosus (SLE). Mycophenolate mofetil (MMF) is an oral immunosuppressive agent used in lupus patients who are intolerant of or refractory to other conventional therapies. The aim of this study was to assess the potential effect of MMF on lowering some biomarkers as a predictive of renal function in patients with Class III LN. Methods: This was a single-center, prospective cohort study that enrolled patients with Class III LN who received 2 g/day of oral MMF. The potential impact of MMF on renal biomarkers was evaluated at baseline and subsequently at 3-month intervals for 6 months according to changes in antinuclear antibodies (ANA), antidouble stranded deoxyribonucleic acid (anti-dsDNA), elastase α-1 proteinase inhibitor (α-1 PI), proteinuria, and the urine protein-to-creatinine ratio (P/C ratio). Results: A significant decrease over the course of MMF treatment compared to the baseline regarding ANA (1.37 ± 0.47 vs. 2.90 ± 1.05, P = 0.03); anti-dsDNA (23.39 ± 3.19 vs. 39.91 ± 8.1 IU/mL, P = 0.02); elastase α-1 PI (512.4 ± 74.12 vs. 696.35 ± 105.35 ng/mL, P = 0.03); proteinuria (0.25 ± 0.44 vs. 1.95 ± 0.76 g/24 h., P = 0.01); and P/C ratio (0.20 ± 0.22 vs. 1.37 ± 0.26, P = 0.04). Conclusion: MMF is effective in lowering renal biomarkers of Class III LN revealed by a significant reduction in ANA, anti-dsDNA, elastase α-1 PI, proteinuria, and P/C ratio over 6 months of MMF treatment.

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The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis

Cited by 3 publications

References 40 publications

Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy

Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy

Correlative multiphoton-STED microscopy of podocyte calcium levels and slit diaphragm ultrastructure in the renal glomerulus

Assessment of the Potential Impact of Mycophenolate Mofetil on Lowering Renal Biomarkers in Patients with Class III Lupus Nephritis: A Pilot Study to Predict Renal Function Progress

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