Kidney Week

Abstract: SA-PO133

Stearyl-Coenzyme A Desaturase 1 Regulates Tubular Cells Mitochondrial Homeostasis Exacerbates AKI

Session Information

• AKI: Metabolism and Cell Death
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Wu, Han, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Han Wu

• Li, Ying, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Ying Li

• Gu, Mengru, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Mengru Gu

• Dai, Chunsun, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Chunsun Dai, MD, PhD

Background

Acute kidney injury is a common clinical acute and critical condition, which is associated with increased mortality, prolonged hospital stay, and the risk of chronic kidney disease (CKD). Numerous studies have shown that renal tubular cell injury and death are the core events of AKI. The kidney is a high energy-consuming organ, and fatty acids become the preferred energy source for renal tubular cells due to their high performance, so mitochondrial dysfunction may be the main cause of renal tubular cell injury during AKI. SCD1 is a key enzyme in lipogenesis, mainly catalyzing production of monounsaturated fatty acids (MUFAs). Previous studies found that SCD1 may play an important role in maintaining mitochondrial homeostasis by participating in lipid metabolism, so we aimed to study whether SCD1 can participate in AKI by regulating mitochondrial homeostasis in tubular cells.

Methods

In vivo, we used SCD1 global knockout mice to construct ischemia-reperfusion-induced acute kidney injury model to study the role of SCD1 in AKI. In vitro, We primarily used primary tubular epithelial cells extracted from SCD1 knockout mice with H₂O₂ treatment and the role of SCD1 in AKI by metabolomics, proteomics, and transcriptomic methods.

Results

Firstly, we found that SCD1 mainly was expressed in the S3 tubular epithelial cells increased significantly during acute kidney injury. Further research showed that SCD1 knockout or inhibiting SCD1 significantly alleviated ischemia-reperfusion-induced acute kidney injury and H₂O₂-induced tubular cell death. Secondly, the results of electron microscopy showed that after H₂O₂ treatment, mitochondrial crest in SCD1 -/- tubular cells was more intensive and the mitochondrial structure was more complete. Thirdly, the metabolomics data demonstrated that SCD1 knockout significantly altered the tubular cells metabolic profile, in which the TCA cycle equivalent significantly increased. The data from transcriptomics and proteomics suggested that knocking out SCD1 significantly upregulated the mitochondrial oxidative phosphorylation proteins relative mRNA and protein expression.

Conclusion

Stearyl-Coenzyme A desaturase SCD1 aggravates acute kidney injury by regulating mitochondrial structure and function.

Funding

• Government Support – Non-U.S.