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Sulforaphane ameliorated podocyte injury according to regulation of the Nrf2/PINK1 pathway for mitophagy in diabetic kidney disease.
- Source :
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European Journal of Pharmacology . Nov2023, Vol. 958, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
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Abstract
- Mitophagy, a mechanism of self-protection against oxidative stress, plays a critical role in podocyte injury caused by diabetic kidney disease (DKD). Sulforaphane (SFN), an isothiocyanate compound, is a potent antioxidant that affords protection against diabetes mellitus-mediated podocyte injury. However, its role and underlying mechanism in DKD especially in diabetic podocytopathy is not clearly defined. In the current study, we demonstrated SFN remarkably activated mitophagy in podocytes, restored urine albumin to creatinine ration, and prevented the glomerular hypertrophy and extensive foot process fusion in diabetic mice. Simultaneously, nephroprotective effects of SFN on kidney injury were abolished in podocyte-specific Nuclear factor erythroid 2-related factor 2 (Nrf2) conditional knockout mouse (cKO), indicating that SFN alleviating DM-induced podocyte injury dependent on Nrf2. In vitro study, supplement with SFN augmented the expression of PTEN induced kinase 1(PINK1) and mediated the activation of mitophagy in podocytes treated with high glucose. Further study revealed that SFN treatment enabled Nrf2 translocate into nuclear and bind to the specific site of PINK1 promoter, ultimately reinforcing the transcription of PINK1. Moreover, SFN failed to confer protection to podocytes treated with high glucose in presence of PINK1 knockdown. On the contrary, exogenous overexpression of PINK1 reversed mitochondrial abnormalities in Nrf2 cKO diabetic mice. In conclusion, SFN alleviated podocyte injury in DKD through activating Nrf2/PINK1 signaling pathway and balancing mitophagy, thus maintaining the mitochondrial homeostasis. • SFN obviously improved renal function and minimized pathological alterations in the glomerulus of diabetic mice. • PINK1 mediated mitophagy in podocytes through enhancing Nrf2 nuclear import. • SFN exerted protective effects on podocyte injury in DKD via mitochondria quality control through Nrf2/PINK1 pathway. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DIABETIC nephropathies
*NUCLEAR factor E2 related factor
*SULFORAPHANE
Subjects
Details
- Language :
- English
- ISSN :
- 00142999
- Volume :
- 958
- Database :
- Academic Search Index
- Journal :
- European Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 172844900
- Full Text :
- https://doi.org/10.1016/j.ejphar.2023.176042