Klotho is regulated by transcription factor Sp1 in renal tubular epithelial cells

BMC Molecular and Cell Biology

article

Li, Yan¹  Liu, Chi¹  He, Ting¹  Bi, Xianjin¹  Zhang, Jingbo¹  Zhang, Bo¹  Zhao, Jinghong¹  Liu, Yong¹  Wang, Kailong¹  Huang, Yinghui¹  Han, Wenhao¹  Xiong, Jiachuan¹  Yang, Ke¹  Liu, Mingying¹  Xiao, Tangli¹ 

[1] Department of Nephrology, the key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University)

关键词: Sp1;    Klotho;    Transcriptional regulation;    Renal tubular epithelial cells;   

DOI  :  10.1186/s12860-020-00292-z

学科分类：内科医学

来源: Colegio Oficial de Psicologos

【 摘 要 】

Klotho is a multifunctional protein, which exists both in a membrane bound and a soluble form. In renal tubules, Klotho is involved in cell senescence, anti-oxidant response, and renal fibrosis, thus regulation of its expression is critical to understand its roles in renal diseases. Indeed, reduced expression was observed in various renal disease. However, the mechanisms underlying transcriptional regulation of the human klotho gene (KL) largely remain unknown. Here we demonstrated that the Klotho expression in human renal tubular epithelial cells (RTECs) was enhanced by overexpression of the transcription factor Sp1. On the contrary, Klotho expression was decreased by Sp1 knockdown. Besides, increased expression of Sp1 alleviated TGF-β1-induced fibrosis in HK-2 cells by inducing Klotho expression. Luciferase reporter assays and chromatin immunoprecipitation assays further identified the binding site of Sp1 was located in − 394 to − 289 nt of the KL promoter, which was further confirmed by mutation analysis. These data demonstrate that KL is a transcriptional target of Sp1 and TGF-β1-induced fibrosis was alleviated by Sp1 in human RTECs by directly modulating Klotho expression, which help to further understand the transcriptional regulation of Klotho in renal disease models.

【 授权许可】

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