ArticleCell death & disease2024
HIF-1α participates in the regulation of S100A16-HRD1-GSK3β/CK1α pathway in renal hypoxia injury.
Article in Cell death & disease, 2024. 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.
- Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism.Annals of medicine · 2026Review
- Transient acute kidney injury following femoral fracture in mice : the role of sympathetic activation.Bone & joint research · 2026Article
- Hesperetin alleviates cerebral ischemia-reperfusion injury by suppressing neuronal ferroptosis.Scientific reports · 2026Article
- Integrative machine learning of hypoxia and centrosome-related gene signatures enables prognostic stratification and therapeutic insights in lung adenocarcinoma.Translational cancer research · 2026Article
- Loss of SEL1L or Hrd1 increases intrinsic LOX levels in HEK293 cells independently of proteasomal degradation.Molecular biology reports · 2026Article
- Renal-targeted exosomes inhibiting miR-182-5p for treatment of renal ischemia-reperfusion injury.Bioengineering & translational medicine · 2026Article
- Salidroside Alleviates Renal Ischemia-reperfusion Injury by Inhibiting Macrophage Pyroptosis Through HIF Signaling.Inflammation · 2025Article
- MYC affects mitochondrial function in IgA nephropathy by promoting the degradation of MFN1 through HRD1.Immunologic research · 2025Article
- Glutathione mitigates hypoxia-induced gill damage in juvenile grass carp (Ctenopharyngodon idellus) by alleviating endoplasmic reticulum stress and autophagy.Journal of animal science and biotechnology · 2025Article
- Acute kidney injury: pathogenesis and therapeutic interventions.Molecular biomedicine · 2025Review
- Expression characteristics of dual-specificity phosphatase 2 and hypoxia-inducible factor-1α in acute kidney injury and preliminary study of the effect of dual-specificity phosphatase 2 on HK-2 cells.Experimental physiology · 2025Article
- Validation ofJournal of thoracic disease · 2025Article
- Targeting endoplasmic reticulum stress-induced CLGN resensitizes hepatocellular carcinoma to apoptosis: paeonol synergistically enhances efficacy by dual inhibition of CLGN and NF-κB.Frontiers in oncology · 2025Article
- Mechanisms and therapeutic prospects of hypoxia-inducible factor 1-alpha in acute kidney injury: a systematic review.Frontiers in cell and developmental biology · 2025Review
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Abstract
S100 calcium-binding protein 16 (S100A16) is implicated in both chronic kidney disease (CKD) and acute kidney injury (AKI). Previous research has shown that S100A16 contributes to AKI by facilitating the ubiquitylation and degradation of glycogen synthase kinase 3β (GSK3β) and casein kinase 1α (CK1α) through the activation of HMG-CoA reductase degradation protein 1 (HRD1). However, the mechanisms governing S100A16-induced HRD1 activation and the upregulation of S100A16 expression in renal injury are not fully understood. In this study, we observed elevated expression of Hypoxia-inducible Factor 1-alpha (HIF-1α) in the kidneys of mice subjected to ischemia-reperfusion injury (IRI). S100A16 deletion attenuated the increased HIF-1α expression induced by IRI. Using a S100A16 knockout rat renal tubular epithelial cell line (NRK-52E cells), we found that S100A16 knockout effectively mitigated apoptosis during hypoxic reoxygenation (H/R) and cell injury induced by TGF-β1. Our results revealed that H/R injuries increased both protein and mRNA levels of HIF-1α and HRD1 in renal tubular cells. S100A16 knockout reversed the expressions of HIF-1α and HRD1 under H/R conditions. Conversely, S100A16 overexpression in NRK-52E cells elevated HIF-1α and HRD1 levels. HIF-1α overexpression increased HRD1 and β-catenin while decreasing GSK-3β. HIF-1α inhibition restored HRD1 and β-catenin upregulation and GSK-3β downregulation by cellular H/R injury. Notably, Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated HIF-1α binding signals on the HRD1 promoter, and luciferase reporter gene assays confirmed HIF-1α's transcriptional regulation of HRD1. Additionally, we identified Transcription Factor AP-2 Beta (TFAP2B) as the upregulator of S100A16. ChIP and luciferase reporter assays confirmed TFAP2B as a transcription factor for S100A16. In summary, this study identifies TFAP2B as the transcription factor for S100A16 and demonstrates HIF-1α regulation of HRD1 transcription within the S100A16-HRD1-GSK3β/CK1α pathway during renal hypoxia injury. These findings provide crucial insights into the molecular mechanisms of kidney injury, offering potential avenues for therapeutic intervention.
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