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논문분류	춘계학술대회 초록집
제목	Autophagy deficiency in endothelial cells increases the susceptibility of renal injury from aging
저자	Sun Ah Nam2, Wan-Young Kim2, Bum Soon Choi3, Jin-Won Kim2, Cheol Whee Park3, Chul Woo Yang3, Jin Kim2, Yong Kyun Kim1
출판정보	2018; 2018(1):
키워드	autophagy \| kidney \| endothelial cell \| aging \| oxidative stress
초록	Objectives: Autophagy is a cellular process of lysosomal degradation of damaged cytoplasmic components and regulates cell death and proliferation. Dysregulation of autophagy in podocytes is involved in the pathogenesis of renal aging. Endothelial cell senescence mediates endothelial damage and may influence maintain of the integrity of glomerular capillary. However, the influence of autophagy in endothelial cells on renal aging remains unclear. In this study, we investigated the role of autophagy in endothelial cells on renal aging using conditional knockout mice in which Atg7 was genetically ablated specifically in endothelial cells. Methods: Atg7flox/flox mice were crossed with Tie2-Cre mice to generate endothelial cells-specific Atg7 knockout mice (Atg7flox/flox;Tie2-Cre mice). Atg7flox/flox litermates served as controls. Mice were sacrificed at the age of 12 months. Results: In wild-type (WT) mice, autophagic flux was increased in aging kidneys compared with young kidneys, however the induction of autophagy was decreased in old-aged Atg7flox/flox;Tie2-Cre mice than old-aged WT mice. Genetic deletion of Atg7 specifically in endothelial cells led to a glomerulopathy with mesangial expansion, capillary wall dilatation, thickness of glomerular basement membrane, foot process effacement and glomerlosclerosis in aging mice that was accompanied by accumulation of reactive oxygen species, transforming growth factor β and interleukin-1-β in glomerulus. Endothelial cells-specific Atg7 deletion induced podocyte loss and proteinuria in aging mice. Conclusions: In summary, our data showed that autophagy in endothelial cells play a protective role in renal aging and the regulation of endothelial autophagy may be a therapeutic target to reduce the injury from renal aging.
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