Skip to main content
Top
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Research

Mitofusin2 expression is associated with podocyte injury in IgA nephropathy

Authors: Xuanli Tang, Yuan Yuan, Xiaoli Liang, Xue Jiang

Published in: European Journal of Medical Research | Issue 1/2023

Login to get access

Abstract

Background

Podocyte injury is associated with IgA nephropathy (IgAN) prognosis. Mitochondrial dysfunction is a major contributor to podocyte injury and death. Mitofusin2 (Mfn2) plays an important role in regulating the morphology and function of mitochondria. This study aimed to investigate the potential of Mfn2 as a biomarker to evaluate the degree of podocyte injury.

Methods

This single-center, retrospective study enrolled 114 patients with biopsy-proven IgAN. Immunofluorescence and TUNEL staining were applied, and clinical and pathological features were compared between patients with different patterns of Mfn2 expression.

Results

In IgAN, Mfn2 is mainly expressed in podocytes and significantly associated with nephrin, TUNEL, and Parkin staining. Among the 114 IgAN patients, 28 (24.56%) did not exhibit Mfn2 expression in podocytes. The patients in the Mfn2-negative group had lower serum albumin (34.43 ± 4.64 g/L vs. 36.48 ± 3 .52 g/L, P = 0.015) and estimated glomerular filtration rate (eGFR) (76.59 ± 35.38 mL/min vs. 92.13 ± 25.35 mL/min, P = 0.013), higher 24 h proteinuria (2.48 ± 2.72 g/d vs. 1.27 ± 1.31 g/d, P = 0.002), serum creatinine (Scr) (107.39 ± 57.97 μmol/L vs. 84.70 ± 34.95 μmol/L, P = 0.015), blood urea nitrogen (BUN) (7.36 ± 4.45 mmol/L vs. 5.68 ± 2.14 mmol/L, P = 0.008), and higher S/T scores (92.86% vs. 70.93% and 42.85% vs. 15.12%, respectively, P < 0.05).
In the Mfn2-negative group, the mitochondria were punctate and round ridges disappeared, and a lower length-to-width ratio and much higher M/A ratio were observed. Correlation analysis showed that the intensity of Mfn2 was negatively correlated with Scr (r = − 0.232, P = 0.013), 24 h proteinuria (r = − 0.541, P = 0.001), and the degree of podocyte effacement (r = − 0.323, P = 0.001), and positively correlated with eGFR (r = 0.213, P = 0.025).
Logistic regression analysis showed that the Mfn2-negative group had a higher risk of severe podocyte effacement (≥ 50%) (OR = 3.061, P = 0.019).

Conclusion

Mfn2 was negatively correlated with proteinuria and renal function. A lack of Mfn2 in podocytes indicates severe podocyte injury and a high degree of podocyte effacement.
Literature
1.
go back to reference Wyatt RJ, Julian BA. IgA nephropathy. N Eng l J Med. 2013;368(25):2402–14.CrossRef Wyatt RJ, Julian BA. IgA nephropathy. N Eng l J Med. 2013;368(25):2402–14.CrossRef
2.
go back to reference Le W, Liang S, Hu Y, et al. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant. 2012;27(4):1479–85.CrossRefPubMed Le W, Liang S, Hu Y, et al. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant. 2012;27(4):1479–85.CrossRefPubMed
3.
go back to reference Hill GS, Karoui KE, Karras A, Mandet C, Van Huyen JPD, Nochy D, Bruneval P. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies. Kidney Int. 2011;79:635–42.CrossRefPubMed Hill GS, Karoui KE, Karras A, Mandet C, Van Huyen JPD, Nochy D, Bruneval P. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies. Kidney Int. 2011;79:635–42.CrossRefPubMed
4.
go back to reference El Karoui K, Hill GS, Karras A, Moulonguet L, Caudwell V, Loupy A, Bruneval P, Jacquot C, Nochy D. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies. Kidney Int. 2011;79:643–54.CrossRefPubMed El Karoui K, Hill GS, Karras A, Moulonguet L, Caudwell V, Loupy A, Bruneval P, Jacquot C, Nochy D. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies. Kidney Int. 2011;79:643–54.CrossRefPubMed
5.
go back to reference Cook HT. Focal segmental glomerulosclerosis in IgA nephropathy: a result of primary podocyte injury? Kidney Int. 2011;79:581–3.CrossRefPubMed Cook HT. Focal segmental glomerulosclerosis in IgA nephropathy: a result of primary podocyte injury? Kidney Int. 2011;79:581–3.CrossRefPubMed
6.
go back to reference Carney EF. Glomerular disease: autophagy failure and mitochondrial dysfunction in FSGS. Nat Rev Nephrol. 2015;11(2):66.PubMed Carney EF. Glomerular disease: autophagy failure and mitochondrial dysfunction in FSGS. Nat Rev Nephrol. 2015;11(2):66.PubMed
7.
go back to reference Arif E, Solanki AK, Srivastava P, Rahman B, Fitzgibbon WR, Deng P, et al. Mitochondrial biogenesis induced by the β2-adrenergic receptor agonist formoterol accelerates podocyte recovery from glomerular injury. Kidney Int. 2019;96:656–73.CrossRefPubMedPubMedCentral Arif E, Solanki AK, Srivastava P, Rahman B, Fitzgibbon WR, Deng P, et al. Mitochondrial biogenesis induced by the β2-adrenergic receptor agonist formoterol accelerates podocyte recovery from glomerular injury. Kidney Int. 2019;96:656–73.CrossRefPubMedPubMedCentral
13.
17.
go back to reference Trimarchi H, Barratt J, Cattran DC, et al. Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int. 2017;91(5):1014–21.CrossRefPubMed Trimarchi H, Barratt J, Cattran DC, et al. Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int. 2017;91(5):1014–21.CrossRefPubMed
19.
go back to reference Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189:211–21.CrossRefPubMedPubMedCentral Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189:211–21.CrossRefPubMedPubMedCentral
20.
go back to reference Santel A, Fuller MT. Control of mitochondrial morphology by a human mitofusin. J Cell Sci. 2001;114(Pt 5):867–74.CrossRefPubMed Santel A, Fuller MT. Control of mitochondrial morphology by a human mitofusin. J Cell Sci. 2001;114(Pt 5):867–74.CrossRefPubMed
22.
go back to reference Lai KN, Leung JC, Chan LY, Saleem MA, Mathieson PW, Tam KY, Xiao J, Lai FM. TangSC: Podocyte injury induced by mesangial derived cytokines in IgA nephropathy. Nephrol Dial Transplant. 2009;24:62–72.CrossRefPubMed Lai KN, Leung JC, Chan LY, Saleem MA, Mathieson PW, Tam KY, Xiao J, Lai FM. TangSC: Podocyte injury induced by mesangial derived cytokines in IgA nephropathy. Nephrol Dial Transplant. 2009;24:62–72.CrossRefPubMed
23.
go back to reference Kang YS, Li Y, Dai C, Kiss LP, Wu C, Liu Y. Inhibition of integrin-linked kinase blocks podocyte epithelial-mesenchymal transition and ameliorates proteinuria. Kidney Int. 2010;78:363–73.CrossRefPubMedPubMedCentral Kang YS, Li Y, Dai C, Kiss LP, Wu C, Liu Y. Inhibition of integrin-linked kinase blocks podocyte epithelial-mesenchymal transition and ameliorates proteinuria. Kidney Int. 2010;78:363–73.CrossRefPubMedPubMedCentral
24.
go back to reference Lemley KV, Lafayette RA, Safai M, Derby G, Blouch K, Squarer A, Myers BD. Podocytopenia and disease severity in IgA nephropathy. Kidney Int. 2002;61:1475–85.CrossRefPubMed Lemley KV, Lafayette RA, Safai M, Derby G, Blouch K, Squarer A, Myers BD. Podocytopenia and disease severity in IgA nephropathy. Kidney Int. 2002;61:1475–85.CrossRefPubMed
25.
go back to reference Xu L, Yang HC, Hao CM, Lin ST, Gu Y, Ma J. Podocyte number predicts progression of proteinuria in IgA nephropathy. Mod Pathol. 2010;23:1241–50.CrossRefPubMed Xu L, Yang HC, Hao CM, Lin ST, Gu Y, Ma J. Podocyte number predicts progression of proteinuria in IgA nephropathy. Mod Pathol. 2010;23:1241–50.CrossRefPubMed
Metadata
Title
Mitofusin2 expression is associated with podocyte injury in IgA nephropathy
Authors
Xuanli Tang
Yuan Yuan
Xiaoli Liang
Xue Jiang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01107-5

Other articles of this Issue 1/2023

European Journal of Medical Research 1/2023 Go to the issue