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Int J Biol Sci 2022; 18(15):5624-5640. doi:10.7150/ijbs.75994 This issue Cite

Research Paper

Regulation of Podocyte Injury by CircHIPK3/FUS Complex in Diabetic Kidney Disease

Feng Liu1, Jing Huang1, Chunyun Zhang1, Yaru Xie1, Yiling Cao1, Li Tao1, Hui Tang1, Jihong Lin2, Hans-Peter Hammes2, Kun Huang3, Fan Yi4, Hua Su1✉, Chun Zhang1✉

1. Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
2. 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, Germany.
3. Tongji School of Pharmacy, Tongji Medical College, Huazhong University of science and Technology, Wuhan 430030, China.
4. Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China.

✉ Corresponding authors: Chun Zhang (E-mail: drzhangchunedu.cn). Address: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Tel: 86-027-85726006, Fax: 86-027-836 More

Citation:
Liu F, Huang J, Zhang C, Xie Y, Cao Y, Tao L, Tang H, Lin J, Hammes HP, Huang K, Yi F, Su H, Zhang C. Regulation of Podocyte Injury by CircHIPK3/FUS Complex in Diabetic Kidney Disease. Int J Biol Sci 2022; 18(15):5624-5640. doi:10.7150/ijbs.75994. https://www.ijbs.com/v18p5624.htm
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Abstract

Graphic abstract

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus and is one of the leading causes of end-stage kidney disease. Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs that play important roles in various diseases, yet their roles in DKD are poorly understood. CircRNA HIPK3 (circHIPK3), a highly conserved circRNA, is closely related to various cellular functions, including cell proliferation and apoptosis. The association between circHIPK3 and diabetic complications has been well demonstrated in multiple previous studies. However, the role of circHIPK3 in podocyte injury in DKD remains unclear. Herein, we discovered that circHIPK3 expression is markedly elevated in cultured podocytes under high-glucose (HG) conditions and glomeruli of diabetic mice, which is closely associated with podocyte injury in DKD. Functionally, lentivirus-mediated knockdown of circHIPK3 dramatically suppresses HG-induced podocyte apoptosis in vitro. Therapeutically, silencing circHIPK3 by adeno-associated virus-mediated RNA interference ameliorates podocyte injury and albuminuria in STZ-induced diabetic mice. Mechanistically, circHIPK3 facilitates the enrichment of fused in sarcoma (FUS) on the ectodysplasin A2 receptor (EDA2R) promoter, resulting in the upregulation of EDA2R expression and activation of apoptotic signaling. Taken together, these results indicate circHIPK3/FUS/EDA2R axis as a therapeutic target for podocyte injury and DKD progression.

Keywords: podocyte injury, diabetic kidney diseases, circHIPK3, FUS, EDA2R

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APA
Liu, F., Huang, J., Zhang, C., Xie, Y., Cao, Y., Tao, L., Tang, H., Lin, J., Hammes, H.P., Huang, K., Yi, F., Su, H., Zhang, C. (2022). Regulation of Podocyte Injury by CircHIPK3/FUS Complex in Diabetic Kidney Disease. International Journal of Biological Sciences, 18(15), 5624-5640. https://doi.org/10.7150/ijbs.75994.

ACS
Liu, F.; Huang, J.; Zhang, C.; Xie, Y.; Cao, Y.; Tao, L.; Tang, H.; Lin, J.; Hammes, H.P.; Huang, K.; Yi, F.; Su, H.; Zhang, C. Regulation of Podocyte Injury by CircHIPK3/FUS Complex in Diabetic Kidney Disease. Int. J. Biol. Sci. 2022, 18 (15), 5624-5640. DOI: 10.7150/ijbs.75994.

NLM
Liu F, Huang J, Zhang C, Xie Y, Cao Y, Tao L, Tang H, Lin J, Hammes HP, Huang K, Yi F, Su H, Zhang C. Regulation of Podocyte Injury by CircHIPK3/FUS Complex in Diabetic Kidney Disease. Int J Biol Sci 2022; 18(15):5624-5640. doi:10.7150/ijbs.75994. https://www.ijbs.com/v18p5624.htm

CSE
Liu F, Huang J, Zhang C, Xie Y, Cao Y, Tao L, Tang H, Lin J, Hammes HP, Huang K, Yi F, Su H, Zhang C. 2022. Regulation of Podocyte Injury by CircHIPK3/FUS Complex in Diabetic Kidney Disease. Int J Biol Sci. 18(15):5624-5640.

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