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Theranostics 2020; 10(16):7465-7479. doi:10.7150/thno.45003 This issue Cite

Research Paper

Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes

Qian Yang1,2*, Jijia Hu1,2*, Yingjie Yang2, Zhaowei Chen1,2, Jun Feng1,2, Zijing Zhu1,2, Huiming Wang1,2, Dingping Yang1,2, Wei Liang1,2, Guohua Ding1,2✉

1. Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
2. Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, China.
*Co-first authors.

✉ Corresponding author: Guohua Ding, MD, PhD, Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China, E-mail: ghxdingcom.

Citation:
Yang Q, Hu J, Yang Y, Chen Z, Feng J, Zhu Z, Wang H, Yang D, Liang W, Ding G. Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes. Theranostics 2020; 10(16):7465-7479. doi:10.7150/thno.45003. https://www.thno.org/v10p7465.htm
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Abstract

Graphic abstract

Disturbed renal lipid metabolism, especially cholesterol dysregulation plays a crucial role in the pathogenesis of chronic kidney disease (CKD). We recently reported that angiotensin (Ang) II could induce cholesterol accumulation and injury in podocytes. However, the underlying mechanisms for these alterations remain unknown.

Methods: Bioinformatics analysis of renal biopsy specimens from patients with hypertensive nephropathy (HN) suggests the involvement of Sirtuin 6 (Sirt6) in Ang II-induced dysregulation of glomerular cholesterol. Using a podocyte-specific Sirt6 knockout mouse model, the effects of Sirt6 on Ang II-induced cholesterol accumulation in podocytes and the therapeutic efficacies of cholesterol-lowering agents were evaluated.

Results: Cholesterol accumulation was detected in the podocytes of Ang II-infused mice, whereas selective deletion of Sirt6 in podocytes not only increased cholesterol accumulation in these cells but also exacerbated Ang II-induced kidney injury. Deletion of Sirt6 also attenuated the protective effect of cyclodextrin (CD) on Ang II-induced urinary albumin excretion, glomerulosclerosis and podocyte injury. In addition, we demonstrated that Sirt6 affected cholesterol efflux in podocytes by regulating the expression of ATP-binding cassette transporter G1 (ABCG1).

Conclusions: These findings provide evidence that Sirt6 is a potential target for renin-angiotensin system (RAS)-associated podocyte injury and provide a rationale for the application of cholesterol-lowering agents in patients with CKD.

Keywords: Sirt6, angiotensin II, cholesterol accumulation, podocyte injury, methyl-β-cyclodextrin

Citation styles

APA
Yang, Q., Hu, J., Yang, Y., Chen, Z., Feng, J., Zhu, Z., Wang, H., Yang, D., Liang, W., Ding, G. (2020). Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes. Theranostics, 10(16), 7465-7479. https://doi.org/10.7150/thno.45003.

ACS
Yang, Q.; Hu, J.; Yang, Y.; Chen, Z.; Feng, J.; Zhu, Z.; Wang, H.; Yang, D.; Liang, W.; Ding, G. Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes. Theranostics 2020, 10 (16), 7465-7479. DOI: 10.7150/thno.45003.

NLM
Yang Q, Hu J, Yang Y, Chen Z, Feng J, Zhu Z, Wang H, Yang D, Liang W, Ding G. Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes. Theranostics 2020; 10(16):7465-7479. doi:10.7150/thno.45003. https://www.thno.org/v10p7465.htm

CSE
Yang Q, Hu J, Yang Y, Chen Z, Feng J, Zhu Z, Wang H, Yang D, Liang W, Ding G. 2020. Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes. Theranostics. 10(16):7465-7479.

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