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Tytuł:
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Sulforaphane suppresses obesity-related glomerulopathy-induced damage by enhancing autophagy via Nrf2.
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Autorzy:
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Lu Y; Department of Nephrology, Second Hospital of Jilin University, Changchun 130041, China.
Zhang Y; Department of Nephrology, Second Hospital of Jilin University, Changchun 130041, China.
Lou Y; Department of Nephrology, Second Hospital of Jilin University, Changchun 130041, China.
Cui W; Department of Nephrology, Second Hospital of Jilin University, Changchun 130041, China. Electronic address: .
Miao L; Department of Nephrology, Second Hospital of Jilin University, Changchun 130041, China. Electronic address: .
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Źródło:
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Life sciences [Life Sci] 2020 Oct 01; Vol. 258, pp. 118153. Date of Electronic Publication: 2020 Jul 29.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
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MeSH Terms:
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Isothiocyanates/*therapeutic use
Kidney Diseases/*drug therapy
Kidney Diseases/*etiology
NF-E2-Related Factor 2/*metabolism
Obesity/*complications
Protective Agents/*therapeutic use
Animals ; Autophagy/drug effects ; Cells, Cultured ; Kidney Diseases/metabolism ; Kidney Glomerulus/cytology ; Kidney Glomerulus/drug effects ; Kidney Glomerulus/metabolism ; Male ; Mice, Inbred C57BL ; Obesity/drug therapy ; Obesity/metabolism ; Podocytes/cytology ; Podocytes/drug effects ; Podocytes/metabolism ; Sulfoxides
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Contributed Indexing:
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Keywords: Autophagy; Metallothionein; Nuclear factor erythroid 2-related factor 2; Obesity-related glomerulopathy; Sulforaphane
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Substance Nomenclature:
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0 (Isothiocyanates)
0 (NF-E2-Related Factor 2)
0 (Nfe2l2 protein, mouse)
0 (Protective Agents)
0 (Sulfoxides)
GA49J4310U (sulforaphane)
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Entry Date(s):
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Date Created: 20200802 Date Completed: 20201007 Latest Revision: 20211204
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Update Code:
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20240104
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DOI:
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10.1016/j.lfs.2020.118153
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PMID:
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32738361
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Aims: Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly with or without focal and segmental glomerulosclerosis lesions. Isothiocyanate sulforaphane (SFN) can protect kidneys from ORG-related damages. In this study, we investigated the effects of SFN as a preventive therapy or intervention for ORG to reveal its mechanism of action.
Main Methods: We established a mouse obesity model with preventive SFN or N-acetylcysteine treatment for 2 months. Thereafter, we used nuclear factor erythroid 2-related factor 2-deficient (Nrf2 -/- ) and wild type mice in our ORG model with SFN treatment. Finally, we generated a corresponding mouse podocyte model in vitro. The body weight, wet weight of perirenal-and peritesticular fat, and urinary albumin/creatinine ratio were assessed. We used periodic acid-Schiff staining and electron microscopy to assess the function of the kidneys and podocytes. In addition, we evaluated the expression of Nrf2 and podocyte-specific proteins by western blotting.
Key Findings: Treatment with SFN reduced body weight, organ-associated fat weight, and urinary albumin/creatinine ratio in both the preventive treatment and disease intervention regimens. SFN treated mice exhibited higher expression levels of podocyte-specific proteins and better podocyte function. However, treatment with SFN did not affect these parameters in obese Nrf2 -/- mice. Light chain 3 of microtubule-associated protein 1-II and metallothionein had higher expression in the wild type than in the Nrf2 -/- mice.
Significance: Treatment with SFN limited ORG-induced damage by enhancing podocyte autophagy via Nrf2.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
