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Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome

Autophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of huma...

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Autores principales: Ogawa-Akiyama, Ayu, Sugiyama, Hitoshi, Kitagawa, Masashi, Tanaka, Keiko, Kano, Yuzuki, Mise, Koki, Otaka, Nozomu, Tanabe, Katsuyuki, Morinaga, Hiroshi, Kinomura, Masaru, Uchida, Haruhito A., Wada, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980606/
https://www.ncbi.nlm.nih.gov/pubmed/31978139
http://dx.doi.org/10.1371/journal.pone.0228337
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author Ogawa-Akiyama, Ayu
Sugiyama, Hitoshi
Kitagawa, Masashi
Tanaka, Keiko
Kano, Yuzuki
Mise, Koki
Otaka, Nozomu
Tanabe, Katsuyuki
Morinaga, Hiroshi
Kinomura, Masaru
Uchida, Haruhito A.
Wada, Jun
author_facet Ogawa-Akiyama, Ayu
Sugiyama, Hitoshi
Kitagawa, Masashi
Tanaka, Keiko
Kano, Yuzuki
Mise, Koki
Otaka, Nozomu
Tanabe, Katsuyuki
Morinaga, Hiroshi
Kinomura, Masaru
Uchida, Haruhito A.
Wada, Jun
author_sort Ogawa-Akiyama, Ayu
collection PubMed
description Autophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of human glomerular diseases is largely unknown. The current study aimed to demonstrate morphological evidence of autophagy and its association with the ultrastructural changes of podocytes and clinical data in patients with idiopathic nephrotic syndrome, a disease in which patients exhibit podocyte injury. The study population included 95 patients, including patients with glomerular disease (minimal change nephrotic syndrome [MCNS], n = 41; idiopathic membranous nephropathy [IMN], n = 37) and 17 control subjects who underwent percutaneous renal biopsy. The number of autophagic vacuoles and the grade of foot process effacement (FPE) in podocytes were examined by electron microscopy (EM). The relationships among the expression of autophagic vacuoles, the grade of FPE, and the clinical data were determined. Autophagic vacuoles were mainly detected in podocytes by EM. The microtubule-associated protein 1 light chain 3 (LC3)-positive area was co-localized with the Wilms tumor 1 (WT1)-positive area on immunofluorescence microscopy, which suggested that autophagy occurred in the podocytes of patients with MCNS. The number of autophagic vacuoles in the podocytes was significantly correlated with the podocyte FPE score (r = -0.443, p = 0.004), the amount of proteinuria (r = 0.334, p = 0.033), and the level of serum albumin (r = -0.317, p = 0.043) in patients with MCNS. The FPE score was a significant determinant for autophagy after adjusting for the age in a multiple regression analysis in MCNS patients (p = 0.0456). However, such correlations were not observed in patients with IMN or in control subjects. In conclusion, the results indicated that the autophagy of podocytes is associated with FPE and severe proteinuria in patients with MCNS. The mechanisms underlying the activation of autophagy in association with FPE in podocytes should be further investigated in order to elucidate the pathophysiology of MCNS.
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spelling pubmed-69806062020-02-04 Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome Ogawa-Akiyama, Ayu Sugiyama, Hitoshi Kitagawa, Masashi Tanaka, Keiko Kano, Yuzuki Mise, Koki Otaka, Nozomu Tanabe, Katsuyuki Morinaga, Hiroshi Kinomura, Masaru Uchida, Haruhito A. Wada, Jun PLoS One Research Article Autophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of human glomerular diseases is largely unknown. The current study aimed to demonstrate morphological evidence of autophagy and its association with the ultrastructural changes of podocytes and clinical data in patients with idiopathic nephrotic syndrome, a disease in which patients exhibit podocyte injury. The study population included 95 patients, including patients with glomerular disease (minimal change nephrotic syndrome [MCNS], n = 41; idiopathic membranous nephropathy [IMN], n = 37) and 17 control subjects who underwent percutaneous renal biopsy. The number of autophagic vacuoles and the grade of foot process effacement (FPE) in podocytes were examined by electron microscopy (EM). The relationships among the expression of autophagic vacuoles, the grade of FPE, and the clinical data were determined. Autophagic vacuoles were mainly detected in podocytes by EM. The microtubule-associated protein 1 light chain 3 (LC3)-positive area was co-localized with the Wilms tumor 1 (WT1)-positive area on immunofluorescence microscopy, which suggested that autophagy occurred in the podocytes of patients with MCNS. The number of autophagic vacuoles in the podocytes was significantly correlated with the podocyte FPE score (r = -0.443, p = 0.004), the amount of proteinuria (r = 0.334, p = 0.033), and the level of serum albumin (r = -0.317, p = 0.043) in patients with MCNS. The FPE score was a significant determinant for autophagy after adjusting for the age in a multiple regression analysis in MCNS patients (p = 0.0456). However, such correlations were not observed in patients with IMN or in control subjects. In conclusion, the results indicated that the autophagy of podocytes is associated with FPE and severe proteinuria in patients with MCNS. The mechanisms underlying the activation of autophagy in association with FPE in podocytes should be further investigated in order to elucidate the pathophysiology of MCNS. Public Library of Science 2020-01-24 /pmc/articles/PMC6980606/ /pubmed/31978139 http://dx.doi.org/10.1371/journal.pone.0228337 Text en © 2020 Ogawa-Akiyama et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ogawa-Akiyama, Ayu
Sugiyama, Hitoshi
Kitagawa, Masashi
Tanaka, Keiko
Kano, Yuzuki
Mise, Koki
Otaka, Nozomu
Tanabe, Katsuyuki
Morinaga, Hiroshi
Kinomura, Masaru
Uchida, Haruhito A.
Wada, Jun
Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome
title Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome
title_full Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome
title_fullStr Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome
title_full_unstemmed Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome
title_short Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome
title_sort podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980606/
https://www.ncbi.nlm.nih.gov/pubmed/31978139
http://dx.doi.org/10.1371/journal.pone.0228337
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