Journal
LIFE SCIENCES
Volume 258, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118153
Keywords
Sulforaphane; Obesity-related glomerulopathy; Nuclear factor erythroid 2-related factor 2; Autophagy; Metallothionein
Funding
- Natural Science Foundation of China [81900384]
- Department of Finance of Jilin Province [2019SRCJ015]
- Jilin Province Science and Technology Development Program [20160414014GH]
- Jilin Province Scientific Research Program [2016446]
- Norman Bethune Program of Jilin University [2015214]
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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.
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