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Negative Regulation of SIRT1 by IRF9 Involved in Hyperlipidemia Acute Pancreatitis Associated with Kidney Injury

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Abstract

Background

Interferon regulatory factor 9 (IRF9) acts as a negative regulator of sirtuin-1 (SIRT1) to participate in many diseases. However, the role of SIRT1 and IRF9 in hyperlipidemia acute pancreatitis associated with kidney injury is unclear.

Aims

To explore the function of SIRT1 and IRF9 in hyperlipidemia acute pancreatitis associated with kidney injury and provide theoretical guidance for disease diagnosis and treatment.

Methods

Model rats were established by intraperitoneal injection of 20% l-arginine. Apoptosis of kidney tissue was determined by TUNEL staining. Expressions of IRF9, SIRT1, p53, and acetylated p53 were detected by qRT-PCR and Western blot. Dual-Luciferase Reporter Assay was carried out to validate the regulation of IRF9 on SIRT1.

Results

Pancreatic and renal injury was more serious, and apoptosis of kidney epithelial cells increased in acute pancreatitis (AP) and hyperlipidemia acute pancreatitis (HLAP) group. IRF9, p53, and acetylated p53 were up-regulated, and SIRT1 was down-regulated in AP and HLAP group (p < 0.05). Down-regulation of SIRT1 was negatively correlated with up-regulation of IRF9 in AP and HLAP group (p < 0.05). Pancreatic and renal injury and kidney epithelial cells apoptosis in HLAP group were more obvious than AP group (p < 0.05). The up-regulation of IRF9 and down-regulation of SIRT1 in HLAP group were more than AP group (p < 0.05). The promoter activity of SIRT1 was repressed by IRF9.

Conclusion

In pancreatitis associated with kidney injury, IRF9 was a negative regulator of SIRT1, down-regulated the expression of SIRT1, increased acetylated p53, and promoted renal cell apoptosis. Hyperlipidemia further aggravated pancreatic and renal injury and renal cell apoptosis.

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Acknowledgments

This work was supported by National Natural Science Foundation Incubation plan (Grant No. 2019GQFY03) and the doctoral research fund project of the Second Affiliated Hospital of Anhui Medical University (Grant No. 2014BKJ034).

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Authors and Affiliations

  1. Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China

    Yi Liu, Yun Sun, Bin-Hua Xue, Xiao-Die Wang & Wei-Li Yu

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  1. Yi Liu
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Correspondence to Wei-Li Yu.

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Liu, Y., Sun, Y., Xue, BH. et al. Negative Regulation of SIRT1 by IRF9 Involved in Hyperlipidemia Acute Pancreatitis Associated with Kidney Injury. Dig Dis Sci 66, 1063–1071 (2021). https://doi.org/10.1007/s10620-020-06331-1

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  • DOI: https://doi.org/10.1007/s10620-020-06331-1

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