Fumarate accumulation involved in renal diabetic fibrosis in Goto-Kakizaki rats.

Animals Citric Acid Cycle Diabetic Nephropathies / metabolism Down-Regulation Fibrosis Fumarates / metabolism Kidney / pathology Male Rats
2D-DIGE Diabetic nephropathy Fibrosis Fumarate Goto-Kakizaki rat TCA cycle

Journal

Archives of biochemistry and biophysics
ISSN: 1096-0384
Titre abrégé: Arch Biochem Biophys
Pays: United States
ID NLM: 0372430

Informations de publication

Date de publication:
15 12 2019
Historique:
received: 26 09 2019
revised: 31 10 2019
accepted: 02 11 2019
pubmed: 11 11 2019
medline: 27 3 2020
entrez: 10 11 2019
Statut: ppublish

Résumé

The Goto-Kakizaki (GK) rat is a spontaneous animal model of type 2 diabetes and early stage of diabetic nephropathy. However, the pathophysiological mechanisms contributing to the progression of diabetic nephropathy in GK rats remain unclear. Kidneys from 15-week old male diabetic GK/Jcl rats and age-matched Wistar rats, which have the same genetic background as GK rats, were used. Proteomic analyses of GK and Wistar kidneys were performed using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). Differentially expressed proteins in GK rats were subjected to pathway analysis, and expression levels of hypoxia inducible factor 1α (HIF-1α) and transforming growth factor-β1 (TGF-β1), and fumarate accumulation in GK kidneys were examined. Azan staining and immunohistochemical staining of α-smooth muscle actin were performed in relation to fibrosis in GK kidneys. Proteomic analysis using 2D-DIGE, analysis of fumarate content, and expression analysis of HIF-1α, TGF-β1, and α-smooth muscle actin of GK rat's kidney, suggested the mechanism of fibrosis characterized as two stages in diabetic nephropathy of GK rats. Abnormalities of glucose metabolism such as elevated levels of 2-oxoglutarate dehydrogenase and reduction of fumarate hydratase caused the accumulation of fumarate followed by the upregulation of HIF-1α and TGF-β1 leading to fibrosis in diabetic nephropathy. Alterations in proteins involved in the tricarboxylic acid cycle are associated with fibrosis through fumarate accumulation in diabetic nephropathy of GK rats.

Identifiants

DOI: 10.1016/j.abb.2019.108167 PMID: 31704098
pubmed: 31704098
pii: S0003-9861(19)30843-4
doi: 10.1016/j.abb.2019.108167
pii:
doi:

Substances chimiques

Fumarates 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108167

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Yuri Miura (Y)

Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. Electronic address: miura@center.tmig.or.jp.

Atsuko Hayakawa (A)

Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan; Department of Bioscience and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama, 337-8570, Japan.

Shohei Kikuchi (S)

Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan; Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Hiroki Tsumoto (H)

Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.

Keitaro Umezawa (K)

Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.

Yuko Chiba (Y)

Department of Diabetes, Metabolism, and Endocrinology, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.

Yurie Soejima (Y)

Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Motoji Sawabe (M)

Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Koji Fukui (K)

Department of Bioscience and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama, 337-8570, Japan.

Yoshihiro Akimoto (Y)

Department Anatomy, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan.

Tamao Endo (T)

Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Fumarate accumulation involved in renal...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Cycle citrique › Fumarate accumulation involved in renal...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Complications du diabète › Néphropathies diabétiques › Fumarate accumulation involved in renal...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › Fumarate accumulation involved in renal...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Fumarate accumulation involved in renal...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Acides acycliques › Diacides carboxyliques › Fumarates › Fumarate accumulation involved in renal...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Fumarate accumulation involved in renal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Fumarate accumulation involved in renal...