ArticleBMC molecular and cell biology2020
Klotho is regulated by transcription factor Sp1 in renal tubular epithelial cells.
Article in BMC molecular and cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease.Nature communications · 2026Article
- α -Klotho Promotes Cell Death and Suppresses Inflammation through TNF-Cellular Inhibitor of Apoptosis Protein 1 Signaling in Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026Article
- Klotho deficiency and cognitive impairment in dialysis patients: mechanisms, clinical evidence, and therapeutic implications.Frontiers in aging neuroscience · 2026Review
- Review
- Inflammation-Induced Klotho Deficiency: A Possible Key Driver of Chronic Kidney Disease Progression.International journal of general medicine · 2025Review
- Alteration of chromatin states perturb the transcription regulation of gene during hydronephrosis.Frontiers in genetics · 2025Article
- Sexually dimorphic renal expression of mouse Klotho is directed by a kidney-specific distal enhancer responsive to HNF1b.Communications biology · 2024Article
- STAT4-Mediated Klotho Up-Regulation Contributes to the Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning via Inhibiting Neuronal Pyroptosis.Molecular neurobiology · 2024Article
- Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation.Theranostics · 2024Article
- Exogenous Klotho Extends Survival in COVID-19 Model Mice.Pathogens (Basel, Switzerland) · 2023Article
- Role of Klotho Protein in Neuropsychiatric Disorders: A Narrative Review.Indian journal of clinical biochemistry : IJCB · 2023Review
- Magnesium in renal fibrosis.International urology and nephrology · 2022Review
- CCL5 Suppresses Klotho ExpressionFrontiers in physiology · 2022Article
- Abnormally decreased renal Klotho is linked to endoplasmic reticulum-associated degradation in mice.International journal of medical sciences · 2022Article
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Authors and funding
15 authors at 1 institution in 1 country.
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Abstract
backgroundKlotho 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.
resultsHere 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.
conclusionsThese 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.
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