Calycosin attenuates renal ischemia/reperfusion injury by suppressing NF-κB mediated inflammation via PPARγ/EGR1 pathway

Renal ischemia
DOI: 10.3389/fphar.2022.970616 Publication Date: 2022-10-07T04:28:52Z
ABSTRACT
Renal ischemia reperfusion injury (IRI) is a leading and common cause of acute kidney (AKI), inflammation critical factor in ischemic AKI progression. Calycosin (CAL), major active component Radix astragali, has been reported to have anti-inflammatory effect multiple organs. However, whether CAL can alleviate renal IRI its mechanism remain uncertain. In the present study, model established by bilateral pedicles occlusion for 35 min male C57BL/6 mice, on measured serum creatinine pathohistological assay. Hypoxia/reoxygenation (H/R) stimulated human tubular epithelial cells HK-2 were applied explore regulatory mechanisms CAL. Luciferase reporter assay molecular docking identify CAL's target protein pathway. mice with IRI, dose dependently alleviated decreased nuclear kappa B (NF-κB) mediated inflammatory response. Bioinformatics analysis experiments showed that early growth response 1 (EGR1) increased promoted NF-κB processes, dose-dependably reduced EGR1. Through JASPAR database luciferase assay, peroxisome proliferator-activated receptor γ (PPARγ) was predicted be transcription EGR1 repressed expression cells. could increase PPARγ dependent manner bind stably PPARγ. after H/R, PPARγ, EGR1, inhibited knockdown siRNA transfection abrogated anti-inflammation therapeutic produced protective attenuating via PPARγ/EGR1
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