Work

Cold‐Inducible RNA‐Binding Protein Alleviates Hypertensive Renal Injury Through the KEAP1‐NRF2 Pathway

Year: 2026

Type: article

Abstract: ABSTRACT Angiotensin II (Ang II) plays crucial roles in renal dysfunction, fibrotic changes, apoptosis, and oxidative stress. CIRBP, a cold‐inducible RNA‐binding protein, functions to maintain cellular homeostasis. However, its role in renal damage elicited by Ang II remains unclear. Here, we investigated the mechanisms through which Cirbp overexpression alleviates renal damage caused by Ang II, and Cirbp deletion induces basal renal injury. Transcriptomic analysis identified the involvement of Cirbp in hypertension‐related renal injury. Across the animal and cell models, Cirbp overexpression attenuated Ang II‐induced renal dysfunction, fibrosis, apoptosis, and inflammation, whereas Cirbp deficiency aggravated basal injury and increased renal susceptibility to injury. CIRBP activated the KEAP1‐NRF2 antioxidant pathway to mitigate redox stress. This renoprotective effect was reversed following the application of the NRF2 inhibitor ML385, but was resumed by the NRF2 agonist RA839. Together, CIRBP modulates redox imbalance during Ang II‐mediated renal damage through KEAP1‐NRF2 signaling.

Source: Smart Medicine

DOI: 10.1002/smmd.70062