Antioxidant role of autophagy in maintaining the integrity of glomerular capillaries

Jun Matsuda, Tomoko Namba, Yoshitsugu Takabatake, Tomonori Kimura, Atsushi Takahashi, Takeshi Yamamoto, Satoshi Minami, Shinsuke Sakai, Ryuta Fujimura, Jun ya Kaimori, Isao Matsui, Takayuki Hamano, Yoko Fukushima, Keiko Matsui, Tomoyoshi Soga, Yoshitaka Isaka

研究成果: Article

5 引用 (Scopus)

抄録

Autophagy is a lysosomal degradation system by which cytosolic materials and damaged organelles are broken down into basic components. To explore the physiological role of autophagy in glomerular endothelial cells (GEnCs), we compared the autophagic flux among cells in the kidney under starvation. Inhibition of autophagy by chloroquine administration significantly increased the number of autophagosomes or autolysosomes in GEnCs and proximal tubular cells, but not in podocytes, suggesting that the GEnCs exhibit substantial autophagic activity. Next, we analyzed endothelial and hematopoietic cell-specific atg5-deficient mice (atg5-conditional KO [cKO] mice). Glomeruli of 4-wk-old atg5-cKO mice exhibited slightly distended capillary loops accompanied by an accumulation of reactive oxygen species (ROS). Glomeruli of 8-wk-old atg5-cKO mice showed a lobular pattern with thickening of the capillary loops and mesangial matrix expansion; however, the vasculature of other organs was preserved. The atg5-cKO mice died by 12 wk of age, presumably due to pancytopenia resulting from the defect in their hematopoietic lineages. Therefore, we subjected 4-wk atg5-cKO mice to irradiation followed by bone marrow transplantation from normal littermates. Transplanted mice recapitulated the glomerular phenotypes of the atg5-cKO mice with no obvious histological changes in other organs. Twelve-mo-old transplanted mice developed mesangiolysis and glomerulosclerosis with significant deterioration of kidney function. Administration of N-acetyl-l-cysteine, a ROS scavenger, to atg5-cKO mice rescued the glomerular phenotypes. These data suggest that endothelial autophagy protects glomeruli from oxidative stress and maintains the integrity of glomerular capillaries. Enhancing endothelial autophagy may provide a novel therapeutic approach to minimizing glomerular diseases.

元の言語English
ページ(範囲)53-65
ページ数13
ジャーナルAutophagy
14
発行部数1
DOI
出版物ステータスPublished - 2018 1 2

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Autophagy
Antioxidants
Endothelial Cells
Reactive Oxygen Species
Phenotype
Kidney
Podocytes
Pancytopenia
Chloroquine
Starvation
Bone Marrow Transplantation
Organelles
Cysteine
Oxidative Stress

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

これを引用

Matsuda, J., Namba, T., Takabatake, Y., Kimura, T., Takahashi, A., Yamamoto, T., ... Isaka, Y. (2018). Antioxidant role of autophagy in maintaining the integrity of glomerular capillaries. Autophagy, 14(1), 53-65. https://doi.org/10.1080/15548627.2017.1391428

Antioxidant role of autophagy in maintaining the integrity of glomerular capillaries. / Matsuda, Jun; Namba, Tomoko; Takabatake, Yoshitsugu; Kimura, Tomonori; Takahashi, Atsushi; Yamamoto, Takeshi; Minami, Satoshi; Sakai, Shinsuke; Fujimura, Ryuta; Kaimori, Jun ya; Matsui, Isao; Hamano, Takayuki; Fukushima, Yoko; Matsui, Keiko; Soga, Tomoyoshi; Isaka, Yoshitaka.

:: Autophagy, 巻 14, 番号 1, 02.01.2018, p. 53-65.

研究成果: Article

Matsuda, J, Namba, T, Takabatake, Y, Kimura, T, Takahashi, A, Yamamoto, T, Minami, S, Sakai, S, Fujimura, R, Kaimori, JY, Matsui, I, Hamano, T, Fukushima, Y, Matsui, K, Soga, T & Isaka, Y 2018, 'Antioxidant role of autophagy in maintaining the integrity of glomerular capillaries', Autophagy, 巻. 14, 番号 1, pp. 53-65. https://doi.org/10.1080/15548627.2017.1391428
Matsuda J, Namba T, Takabatake Y, Kimura T, Takahashi A, Yamamoto T その他. Antioxidant role of autophagy in maintaining the integrity of glomerular capillaries. Autophagy. 2018 1 2;14(1):53-65. https://doi.org/10.1080/15548627.2017.1391428
Matsuda, Jun ; Namba, Tomoko ; Takabatake, Yoshitsugu ; Kimura, Tomonori ; Takahashi, Atsushi ; Yamamoto, Takeshi ; Minami, Satoshi ; Sakai, Shinsuke ; Fujimura, Ryuta ; Kaimori, Jun ya ; Matsui, Isao ; Hamano, Takayuki ; Fukushima, Yoko ; Matsui, Keiko ; Soga, Tomoyoshi ; Isaka, Yoshitaka. / Antioxidant role of autophagy in maintaining the integrity of glomerular capillaries. :: Autophagy. 2018 ; 巻 14, 番号 1. pp. 53-65.
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