SNORD3A Regulates STING Transcription to Promote Ferroptosis in Acute Kidney Injury.
Huanhuan ZhuJunni WangJin MiaoMingdi ShenHuijing WangXiaohan HuangAnqi NiHuijuan WuJianghua ChenLiang XiaoShanshan XieWeiqiang LinFei HanPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
Acute kidney injury (AKI) signifies a sudden and prolonged decline in kidney function characterized by tubular cell death and interstitial inflammation. Small nucleolar RNAs (snoRNAs) play pivotal roles in oxidative stress and inflammation, and may play an important role in the AKI process, which remains elusive. an elevated expression of Snord3a is revealed in renal tubules in response to AKI and demonstrates that Snord3a deficiency alleviates renal injury in AKI mouse models. Notably, the deficiency of Snord3a exhibits a mitigating effect on the stimulator of interferon genes (STING)-associated ferroptosis phenotypes and the progression of tubular injury. Mechanistically, Snord3a is shown to regulate the STING signaling axis via promoting STING gene transcription; administration of Snord3a antisense oligonucleotides establishes a significant therapeutic advantage in AKI mouse models. Together, the findings elucidate the transcription regulation mechanism of STING and the crucial roles of the Snord3a-STING axis in ferroptosis during AKI, underscoring Snord3a as a potential prognostic and therapeutic target for AKI.
Keyphrases
- acute kidney injury
- cell death
- cardiac surgery
- oxidative stress
- mouse model
- transcription factor
- genome wide
- poor prognosis
- dna damage
- risk assessment
- cell cycle arrest
- dna methylation
- gene expression
- genome wide identification
- climate change
- high glucose
- long non coding rna
- pi k akt
- heat shock protein
- endoplasmic reticulum stress