ID | 64110 |
フルテキストURL | |
著者 |
Oda, Kaori
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Miyamoto, Satoshi
Center for Innovative Clinical Medicine, Okayama University Hospital
Kaken ID
Wada, Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism
ORCID
Kaken ID
publons
researchmap
Shikata, Kenichi
Center for Innovative Clinical Medicine, Okayama University Hospital
ORCID
Kaken ID
publons
researchmap
|
抄録 | Aims/Introduction Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL-18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL-18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg-A(y)/TaJcl (KK-Ay) mice against DKD progression. Materials and Methods Suramin or saline was administered i.p. to KK-Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin. Results Suramin treatment significantly suppressed the increase in the urinary albumin-to-creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK-Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome-related genes and proteins in the renal cortex of KK-Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK-Ay mice and mainly distributed in the glomerular mesangial cells of KK-Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP-induced NLRP3 complex formation and the downstream expression of caspase-1 and IL-18 in MMCs. Conclusions These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD.
|
キーワード | Diabetic kidney disease
Inflammasomes
Suramin
|
発行日 | 2022-10-29
|
出版物タイトル |
Journal Of Diabetes Investigation
|
巻 | 14巻
|
号 | 2号
|
出版者 | Wiley
|
開始ページ | 205
|
終了ページ | 220
|
ISSN | 2040-1116
|
資料タイプ |
学術雑誌論文
|
言語 |
英語
|
OAI-PMH Set |
岡山大学
|
著作権者 | © 2022 The Authors.
|
論文のバージョン | publisher
|
PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1111/jdi.13930
|
ライセンス | https://creativecommons.org/licenses/by-nc-nd/4.0/
|