ArticleScientific reports2019
Mechanism and Consequences of The Impaired Hif-1α Response to Hypoxia in Human Proximal Tubular HK-2 Cells Exposed to High Glucose.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- The mechanism and therapeutic prospect of HIF-1 α/BNIP3 pathway in regulating mitophagy in tubulointerstitial fibrosis.Renal failure · 2026Review
- Sodium Butyrate Attenuates Renal Fibrosis by Regulating Glycolysis and Histone H4K12 Lactylation in Diabetic Kidney Disease.Diabetes, obesity & metabolism · 2026Article
- MORG1 Haploinsufficiency Is Associated with Stage- and Sex-Dependent Renoprotection and Signalling Alterations in Diabetic Kidney Disease.International journal of molecular sciences · 2026Article
- Feeding the invaders: how metabolic imbalance shapes infection and biofilm development.FEMS microbiology reviews · 2026Review
- Diabetic Kidney Disease: From Pathophysiology to Treatment Perspectives.Kidney & blood pressure research · 2026Review
- Cell-type specific effects of the long non-coding RNA HIF1A-AS3 on HIF1A expression in kidney cells.Scientific reports · 2025Article
- Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathway.Scientific reports · 2025Article
- The role of hypoxia-inducible factors 1 and 2 in the pathogenesis of diabetic kidney disease.Journal of nephrology · 2025Review
- Testicular torsion diagnosis and injury assessment using photoacoustic oxygenation imaging.Photoacoustics · 2023Article
- The "sweet" path to cancer: focus on cellular glucose metabolism.Frontiers in oncology · 2023Review
- Zinc and hypoxic preconditioning: a strategy to enhance the functionality and therapeutic potential of bone marrow-derived mesenchymal stem cells.Molecular and cellular biochemistry · 2022Article
- Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes.Antioxidants (Basel, Switzerland) · 2022Review
- Hypoxia mimetics restore bone biomineralisation in hyperglycaemic environments.Scientific reports · 2022Article
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors.International journal of molecular sciences · 2022Review
- A Glimpse of Inflammation and Anti-Inflammation Therapy in Diabetic Kidney Disease.Frontiers in physiology · 2022Review
- Potential Molecular Mechanism of Yishen Capsule in the Treatment of Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications.Theranostics · 2022Review
- Transcription Factor ChREBP Mediates High Glucose-Evoked Increase in HIF-1α Content in Epithelial Cells of Renal Proximal Tubules.International journal of molecular sciences · 2021Article
- Normalizing HIF-1α Signaling Improves Cellular Glucose Metabolism and Blocks the Pathological Pathways of Hyperglycemic Damage.Biomedicines · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal hypoxia and loss of proximal tubular cells (PTC) are relevant in diabetic nephropathy. Hypoxia inhibits hypoxia-inducible factor-1α (HIF-1α) degradation, which leads to cellular adaptive responses through HIF-1-dependent activation of gene hypoxia-responsive elements (HRE). However, the diabetic microenvironment represses the HIF-1/HRE response in PTC. Here we studied the mechanism and consequences of impaired HIF-1α regulation in human proximal tubular HK-2 cells incubated in hyperglycemia. Inhibition at different levels of the canonical pathway of HIF-1α degradation did not activate the HIF-1/HRE response under hyperglycemia, except when proteasome was inhibited. Further studies suggested that hyperglycemia disrupts the interaction of HIF-1α with Hsp90, a known cause of proteasomal degradation of HIF-1α. Impaired HIF-1α regulation in cells exposed to hyperglycemic, hypoxic diabetic-like milieu led to diminished production of vascular endothelial growth factor-A and inhibition of cell migration (responses respectively involved in tubular protection and repair). These effects, as well as impaired HIF-1α regulation, were reproduced in normoglycemia in HK-2 cells incubated with microparticles released by HK-2 cells exposed to diabetic-like milieu. In summary, these results highlight the role of proteasome-dependent mechanisms of HIF-1α degradation on diabetes-induced HK-2 cells dysfunction and suggest that cell-derived microparticles may mediate negative effects of the diabetic milieu on PTC.
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