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Usage Information

Activation of acetyl-CoA synthetase 2 mediates kidney injury in diabetic nephropathy
Jian Lu, Xue Qi Li, Pei Pei Chen, Jia Xiu Zhang, Liang Liu, Gui Hua Wang, Xiao Qi Liu, Ting Ting Jiang, Meng Ying Wang, Wen Tao Liu, Xiong Zhong Ruan, Kun Ling Ma
Jian Lu, Xue Qi Li, Pei Pei Chen, Jia Xiu Zhang, Liang Liu, Gui Hua Wang, Xiao Qi Liu, Ting Ting Jiang, Meng Ying Wang, Wen Tao Liu, Xiong Zhong Ruan, Kun Ling Ma
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Research Article Metabolism Nephrology

Activation of acetyl-CoA synthetase 2 mediates kidney injury in diabetic nephropathy

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Abstract

Albuminuria and podocyte injury are the key cellular events in the progression of diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is a nucleocytosolic enzyme responsible for the regulation of metabolic homeostasis in mammalian cells. This study aimed to investigate the possible roles of ACSS2 in kidney injury in DN. We constructed an ACSS2-deleted mouse model to investigate the role of ACSS2 in podocyte dysfunction and kidney injury in diabetic mouse models. In vitro, podocytes were chosen and transfected with ACSS2 siRNA and ACSS2 inhibitor and treated with high glucose. We found that ACSS2 expression was significantly elevated in the podocytes of patients with DN and diabetic mice. ACSS2 upregulation promoted phenotype transformation and inflammatory cytokine expression while inhibiting podocytes’ autophagy. Conversely, ACSS2 inhibition improved autophagy and alleviated podocyte injury. Furthermore, ACSS2 epigenetically activated raptor expression by histone H3K9 acetylation, promoting activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Pharmacological inhibition or genetic depletion of ACSS2 in the streptozotocin-induced diabetic mouse model greatly ameliorated kidney injury and podocyte dysfunction. To conclude, ACSS2 activation promoted podocyte injury in DN by raptor/mTORC1-mediated autophagy inhibition.

Authors

Jian Lu, Xue Qi Li, Pei Pei Chen, Jia Xiu Zhang, Liang Liu, Gui Hua Wang, Xiao Qi Liu, Ting Ting Jiang, Meng Ying Wang, Wen Tao Liu, Xiong Zhong Ruan, Kun Ling Ma

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Usage data is cumulative from July 2025 through July 2026.

Usage JCI PMC
Text version 2,469 503
PDF 252 85
Figure 930 16
Supplemental data 261 31
Citation downloads 293 0
Totals 4,205 635
Total Views 4,840

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