2. Academic Validation
  3. SNORD3A Regulates STING Transcription to Promote Ferroptosis in Acute Kidney Injury

SNORD3A Regulates STING Transcription to Promote Ferroptosis in Acute Kidney Injury

  • Adv Sci (Weinh). 2024 Jul 4:e2400305. doi: 10.1002/advs.202400305.
Huanhuan Zhu 1,  Junni Wang 1,  Jin Miao 1,  Mingdi Shen 1,  Huijing Wang 1,  Xiaohan Huang 1,  Anqi Ni 1,  Huijuan Wu 2,  Jianghua Chen 1,  Liang Xiao 1,  Shanshan Xie 3,  Weiqiang Lin 4,  Fei Han 1
Affiliations

Affiliations

  • 1 Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Institute of Nephrology, Zhejiang University, Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, 310003, China.
  • 2 Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
  • 3 Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 310052, China.
  • 4 The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, China.
PMID: 38962954 DOI: 10.1002/advs.202400305
Abstract

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.

Keywords

STING; Snord3a; acute kidney injury; ferroptosis; snoRNA.

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