論文

査読有り
2014年3月

Pemt Deficiency Ameliorates Endoplasmic Reticulum Stress in Diabetic Nephropathy

PLOS ONE
  • Mayu Watanabe
  • ,
  • Atsuko Nakatsuka
  • ,
  • Kazutoshi Murakami
  • ,
  • Kentaro Inoue
  • ,
  • Takahiro Terami
  • ,
  • Chigusa Higuchi
  • ,
  • Akihiro Katayama
  • ,
  • Sanae Teshigawara
  • ,
  • Jun Eguchi
  • ,
  • Daisuke Ogawa
  • ,
  • Eijiro Watanabe
  • ,
  • Jun Wada
  • ,
  • Hirofumi Makino

9
3
開始ページ
e92647
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0092647
出版者・発行元
PUBLIC LIBRARY SCIENCE

Phosphatidylethanolamine N-methyltransferase (Pemt) catalyzes the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) mainly in the liver. Under an obese state, the upregulation of Pemt induces endoplasmic reticulum (ER) stress by increasing the PC/PE ratio in the liver. We targeted the Pemt gene in mice to explore the therapeutic impact of Pemt on the progression of diabetic nephropathy and diabetes, which was induced by the injection of streptozotocin (STZ). Although the blood glucose levels were similar in STZ-induced diabetic Pemt+/+ and Pemt-/-mice, the glomerular hypertrophy and albuminuria in Pemt-/- mice were significantly reduced. Pemt deficiency reduced the intraglomerular F4/80-positive macrophages, hydroethidine fluorescence, tubulointerstitial fibrosis and tubular atrophy. The expression of glucose-regulated protein-78 (GRP78) was enriched in the renal tubular cells in STZ-induced diabetic mice, and this was ameliorated by Pemt deficiency. In mProx24 renal proximal tubular cells, the treatment with ER-stress inducers, tunicamycin and thapsigargin, increased the expression of GRP78, which was reduced by transfection of a shRNA lentivirus for Pemt (shRNA-Pemt). The number of apoptotic cells in the renal tubules was significantly reduced in Pemt-/- diabetic mice, and shRNA-Pemt upregulated the phosphorylation of Akt and decreased the cleavage of caspase 3 and 7 in mProx24 cells. Taken together, these findings indicate that the inhibition of Pemt activity ameliorates the ER stress associated with diabetic nephropathy in a model of type 1 diabetes and corrects the functions of the three major pathways downstream of ER stress, i.e. oxidative stress, inflammation and apoptosis.

Web of Science ® 被引用回数 : 13

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0092647
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000333675600060&DestApp=WOS_CPL
URL
http://orcid.org/0000-0003-1468-5170
ID情報
  • DOI : 10.1371/journal.pone.0092647
  • ISSN : 1932-6203
  • ORCIDのPut Code : 17913046
  • Web of Science ID : WOS:000333675600060

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