4.5 Article

SENP3 Aggravates Renal Tubular Epithelial Cell Apoptosis in Lipopolysaccharide-Induced Acute Kidney Injury via deSUMOylation of Drp1

期刊

KIDNEY DISEASES
卷 8, 期 5, 页码 424-435

出版社

KARGER
DOI: 10.1159/000525308

关键词

SENP3; Lipopolysaccharide; Acute kidney injury; Apoptosis; deSUMOylation; Drp1

资金

  1. National Natural Science Foundation of China [82170696, 81800631]

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The study indicated that SENP3 played a significant regulatory role in LPS-induced AKI, inducing cell apoptosis through protein deSUMOylation and exacerbating damage to renal tubular epithelial cells.
Background: Sepsis causes acute kidney injury (AKI) in critically ill patients, although the mechanisms underlying the pathophysiology are not fully understood. SUMO-specific proteases 3 (SENP3), a member of the deSUMOylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, the role of SENP3 in septic AKI remains unclear. Objectives: The purpose of this study was to investigate the role of SENP3 in lipopolysaccharide (LPS)-induced AKI model. Methods: C57BL/6 mice were given intraperitoneal injection of LPS (10 mg/kg). NRK-52E cells were treated with LPS in vitro. The SENP3 protein expression was analyzed by Western blotting. The levels of reactive oxygen species (ROS) in cells were measured using DCFH-DA. SENP3-siRNA or SENP3-plasmid was, respectively, transfected into NRK-52E cells to knock down or overexpress the SENP3 expression. Western blotting was performed to analyze the protein expression of cleaved caspase 3, cytochrome c, and dynamin-related protein 1 (Drp1). The mitochondrial membrane potential was measured using JC-1 assay kit. Co-immunoprecipitation was used to determine the interaction of Drp1 and SMUO2/3. Results: SENP3 protein expression was obviously increased in renal tissues from the mouse model of LPS-induced AKI. Accordingly, SENP3 expression was upregulated in NRK-52E cells treated with LPS in a ROS-dependent manner in vitro. Knockdown of SENP3 dramatically ameliorated LPS-induced apoptosis of NRK-52E cells, whereas overexpression of SENP3 further aggravated LPS-induced apoptosis of NRK-52E cells. Mechanistically, SENP3 triggered Drp1 recruitment to mitochondria by increasing the deSUMOylation of Drp1. Conclusion: SENP3 aggravated renal tubular epithelial cell apoptosis in LPS-induced AKI via Drp1 deSUMOylation manner.

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