@article{oai:shiga-med.repo.nii.ac.jp:00003513, author = {吉林, 護 and 久米, 真司 and 山原, 真子 and 山原, 康佑 and 武田, 尚子 and 大澤, 紀之 and 金崎, 雅美 and 中江, 由希 and 前川, 聡 and 荒木, 信一 and YOSHIBAYASHI, Mamoru and KUME, Shinji and YASUDA-YAMAHARA, Mako and YAMAHARA, Kosuke and TAKEDA, Naoko and OSAWA, Norihisa and Chin-Kanasaki, Masami and Nakae, Yuki and YOKOI, Hideki and MUKOYAMA, Masashi and ASANUMA, Katsuhiko and MAEGAWA, Hiroshi and ARAKI, Shin-ichi}, issue = {2}, journal = {Biochemical and biophysical research communications}, month = {Apr}, note = {To examine the cell-protective role of podocyte autophagy against glomerular endothelial dysfunction in diabetes, we analyzed the renal phenotype of tamoxifen (TM)-inducible podocyte-specific Atg5-deficient (iPodo-Atg5-/-) mice with experimental endothelial dysfunction. In both control and iPodo-Atg5-/- mice, high fat diet (HFD) feeding induced glomerular endothelial damage characterized by decreased urinary nitric oxide (NO) excretion, collapsed endothelial fenestrae, and reduced endothelial glycocalyx. HFD-fed control mice showed slight albuminuria and nearly normal podocyte morphology. In contrast, HFD-fed iPodo-Atg5-/- mice developed massive albuminuria accompanied by severe podocyte injury that was observed predominantly in podocytes adjacent to damaged endothelial cells by scanning electron microscopy. Although podocyte-specific autophagy deficiency did not affect endothelial NO synthase deficiency-associated albuminuria, it markedly exacerbated albuminuria and severe podocyte morphological damage when the damage was induced by intravenous neuraminidase injection to remove glycocalyx from the endothelial surface. Furthermore, endoplasmic reticulum stress was accelerated in podocytes of iPodo-Atg5-/- mice stimulated with neuraminidase, and treatment with molecular chaperone tauroursodeoxycholic acid improved neuraminidase-induced severe albuminuria and podocyte injury. In conclusion, podocyte autophagy plays a renoprotective role against diabetes-related structural endothelial damage, providing an additional insight into the pathogenesis of massive proteinuria in diabetic nephropathy., Journal Article}, pages = {319--325}, title = {Protective role of podocyte autophagy against glomerular endothelial dysfunction in diabetes.}, volume = {525}, year = {2020} }