Int J Med Sci 2020; 17(17):2850-2860. doi:10.7150/ijms.48429 This issue

Research Paper

Knockdown of CK2α reduces P-cresol-induced fibrosis in human renal proximal tubule epithelial cells via the downregulation of profilin-1

Yeo Min Yoon1, Gyeongyun Go2, Chul Won Yun1, Ji Ho Lim1, Sang Hun Lee1,2✉

1. Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, 04401, Republic of Korea.
2. Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan, 31151, Republic of Korea.

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Citation:
Yoon YM, Go G, Yun CW, Lim JH, Lee SH. Knockdown of CK2α reduces P-cresol-induced fibrosis in human renal proximal tubule epithelial cells via the downregulation of profilin-1. Int J Med Sci 2020; 17(17):2850-2860. doi:10.7150/ijms.48429. Available from https://www.medsci.org/v17p2850.htm

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Abstract

Renal fibrosis is one of the main causes of chronic kidney disease. Many studies have focused on fibroblasts and myofibroblasts involved in renal fibrogenesis. Recently, several studies have reported that renal proximal tubule epithelial cells are possible initiators of renal fibrosis. However, the mechanism through which cells induce renal fibrosis is poorly understood. In this study, we found that CK2α induces fibrosis in renal proximal tubule epithelial cells (TH1) by regulating the expression of profilin-1 (Pfn1). CKD mouse model and TH1 cells treated with P-cresol also showed an increased level of Pfn1. The knockdown of CK2α suppressed fibrosis in TH1 cells via the downregulation of Pfn1. In particular, CK2α knockdown inhibited the expression of stress fibers and fibrosis-related proteins in P-cresol-treated TH1 cells. Furthermore, the knockdown of CK2α inhibited mitochondrial dysfunction and restored cellular senescence and cell cycle in P-cresol-treated TH1 cells. These results indicate that CK2α induces renal fibrosis through Pfn1, which makes CK2α a key target molecule in the treatment of fibrosis related to chronic kidney disease.

Keywords: CK2α, Profilin-1, CKD, fibrosis, stress F-actin, renal proximal tubule epithelial cell