ReferenceID 1216
Involvement of REV-ERBα dysregulation and ferroptosis in aristolochic acid I-induced renal injury
Biochem Pharmacol
The molecular events underlying aristolochic acid (AA) nephropathy are poorly understood, and specific therapies for treatment of AA nephropathy are still lacking. Here we aimed to investigate a potential role of REV-ERB
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 1216
- Evidence Id
- 17806
- Core Evidence Id
- 17806
- Source Reference Id
- 2419
- Herb2 Reference Id
- HBREF003216
- Subject Paper Key
- HBIN016798_34673015
- Pubmed Id
- 34673015
- Doi
- 10.1016/j.bcp.2021.114807
- Paper Title
- Involvement of REV-ERBα dysregulation and ferroptosis in aristolochic acid I-induced renal injury
- Paper Abstract
- The molecular events underlying aristolochic acid (AA) nephropathy are poorly understood, and specific therapies for treatment of AA nephropathy are still lacking. Here we aimed to investigate a potential role of REV-ERBalpha and ferroptosis in renal injury induced by aristolochic acid I (AAI), a typical AA. The regulatory effects of REV-ERBalpha on AAI-induced renal injury were determined using kidney-specific Rev-erbalpha knockout mice. Ferroptosis was assessed based on measurements of iron, GSH, and GPX4. Targeted antagonism of REV-ERBalpha to alleviate AAI-induced renal injury and ferroptosis was assessed using the small molecule antagonist SR8278. mRNAs and proteins were quantified by qPCR and Western blotting, respectively. We first showed that REV-ERBalpha was upregulated and its target BMAL1 was downregulated in the kidney of mice with AAI nephropathy. Upregulation of REV-ERBalpha protein was confirmed in aristolactam I (ALI, a nephrotoxic metabolite of AAI)-treated mRTECs. We also observed enhanced ferroptosis (known to be regulated by REV-ERBalpha) in mice with AAI nephropathy and in ALI-treated mRTECs. Kidney-specific knockout of Rev-erbalpha reduced the sensitivity of mice to AAI-induced ferroptosis and renal injury. Furthermore, knockdown of Rev-erbalpha by siRNA or SR8278 (a REV-ERBalpha antagonist) treatment attenuated ALI-induced ferroptosis in mRTECs. Moreover, REV-ERBalpha antagonism by SR8278 alleviated ferroptosis and renal injury caused by AAI in mice. In conclusion, we identify REV-ERBalpha as a regulator of AAI-induced renal injury via promoting ferroptosis. Targeting REV-ERBalpha may represent a promising approach for management of AAI nephropathy.
- Journal
- Biochem Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Ferroptosis; Renal Injury; Aa Nephropathy; Aristolochic Acid (aa) Nephropathy; Aai Nephropathy
- Paper Title Cn
- Paper Title En
- Involvement of REV-ERBα dysregulation and ferroptosis in aristolochic acid I-induced renal injury
- Bilingual Status
- semi_complete