دورية أكاديمية
أعرض في EDS

Loss of NF-E2 expression contributes to the induction of profibrotic signaling in diabetic kidneys.

التفاصيل البيبلوغرافية
العنوان: Loss of NF-E2 expression contributes to the induction of profibrotic signaling in diabetic kidneys.
المؤلفون: Jin S; Department of Medicine, Division Nephrology, Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA., Li J; Department of Nephrology, the First Hospital of Jilin University, Changchun, Jilin 130021, China; Pediatric Research Institute, Departments of Pediatrics, University of Louisville, Louisville, KY 40292, USA., Barati M; Department of Medicine, Division Nephrology, Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA., Rane S; Department of Medicine, Division Nephrology, Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA., Lin Q; Pediatric Research Institute, Departments of Pediatrics, University of Louisville, Louisville, KY 40292, USA., Tan Y; Pediatric Research Institute, Departments of Pediatrics, University of Louisville, Louisville, KY 40292, USA; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA., Zheng Z; Department of Nephrology, the First Hospital of Jilin University, Changchun, Jilin 130021, China; Pediatric Research Institute, Departments of Pediatrics, University of Louisville, Louisville, KY 40292, USA., Cai L; Pediatric Research Institute, Departments of Pediatrics, University of Louisville, Louisville, KY 40292, USA; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA; Department of Radiation Oncology, University of Louisville, Louisville, KY 40292, USA. Electronic address: L0cai001@louisville.edu., Rane MJ; Department of Medicine, Division Nephrology, Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA. Electronic address: madhavi.rane@louisville.edu.
المصدر: Life sciences [Life Sci] 2020 Aug 01; Vol. 254, pp. 117783. Date of Electronic Publication: 2020 May 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
مواضيع طبية MeSH: Diabetes Mellitus, Experimental/*metabolism , Fibrosis/*physiopathology , NF-E2 Transcription Factor, p45 Subunit/*physiology, Animals ; Cadherins/biosynthesis ; Cells, Cultured ; Cysteine Proteinase Inhibitors/pharmacology ; Diabetes Mellitus, Experimental/genetics ; Down-Regulation ; Fibrosis/metabolism ; Gene Knockdown Techniques ; HSP27 Heat-Shock Proteins/metabolism ; Humans ; Kidney/metabolism ; Kidney Tubules/metabolism ; Leupeptins/pharmacology ; Male ; Mice ; Mice, Transgenic ; NF-E2 Transcription Factor, p45 Subunit/biosynthesis ; NF-E2 Transcription Factor, p45 Subunit/genetics ; Protein Binding/drug effects ; Signal Transduction/physiology ; Transforming Growth Factor beta/adverse effects ; Transforming Growth Factor beta/antagonists & inhibitors
مستخلص: Aims: This study aimed to examine the anti-fibrotic role of Nuclear Factor-Erythroid derived 2 (NF-E2) in human renal tubule (HK-11) cells and in type 1 and type 2 diabetic (T1D, T2D) mouse kidneys.
Main Methods: Anti-fibrotic effects of NF-E2 were examined in transforming growth factor-β (TGF-β) treated HK-11 cells by over-expressing/silencing NF-E2 expression and determining its effects on profibrotic signaling. NF-E2 proteasomal degradation was confirmed by proteasome inhibition in HK-11 cells and diabetic mice. Clinical relevance of changes in NF-E2 expression to fibrotic changes in the kidney were assessed in T1D and T2D mouse kidneys.
Key Findings: NF-E2 expression was significantly decreased in TGF-β treated HK-11 cells and in kidneys of diabetic mice with concurrent increase in expression of fibrotic proteins. TGF-β treatment of HK-11 cells did not inhibit NF-E2 mRNA expression, suggesting that the post-translational changes may contribute to NF-E2 protein degradation. The down-regulation of NF-E2 expression was attributed to its proteasomal degradation, as TGF-β- and diabetes-induced NF-E2 down regulation was prevented by proteasome inhibitor treatment. In HK-11 cells TGF-β treatment decreased E-cadherin expression and induced pSer 82 Hsp27/NF-E2 association, likely to promote NF-E2 degradation, as Hsp27 can target proteins to the proteasome. A critical role for NF-E2 in regulation of renal fibrosis was demonstrated as over-expression of NF-E2 or silencing NF-E2 expression, decreased or increased profibrotic proteins in TGF-β-treated HK-11 cells, respectively.
Significance: NF-E2, a novel anti-fibrotic protein, is down-regulated in diabetic kidneys. Preserving/inducing NF-E2 expression in diabetic kidneys may provide a therapeutic potential to combat DN.
Competing Interests: Declaration of competing interest Authors declare they have no conflict of interest.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Diabetes; Fibrosis; Heat shock protein 27 (Hsp27); Human renal proximal tubule (HK-11) cells; Kidney; Nuclear factor-Erythroid derived 2 (NF-E2); Proteasome; Transforming growth factor β (TGF-β)
المشرفين على المادة: 0 (Cadherins)
0 (Cysteine Proteinase Inhibitors)
0 (HSP27 Heat-Shock Proteins)
0 (Leupeptins)
0 (NF-E2 Transcription Factor, p45 Subunit)
0 (Nfe2 protein, mouse)
0 (Transforming Growth Factor beta)
RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
تواريخ الأحداث: Date Created: 20200516 Date Completed: 20200629 Latest Revision: 20200629
رمز التحديث: 20231215
DOI: 10.1016/j.lfs.2020.117783
PMID: 32413404
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-0631
DOI:10.1016/j.lfs.2020.117783