ArticleThe Journal of pharmacology and experimental therapeutics2012
Impaired wound healing in hypoxic renal tubular cells: roles of hypoxia-inducible factor-1 and glycogen synthase kinase 3β/β-catenin signaling.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- The LC-MS/MS Identification and Analgesic and Wound Healing Activities ofPlants (Basel, Switzerland) · 2022Article
- Susceptibility of renal fibrosis in diabetes: Role of hypoxia inducible factor-1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Chrysin Ameliorates Cyclosporine-A-Induced Renal Fibrosis by Inhibiting TGF-βInternational journal of molecular sciences · 2021Article
- Promotion of β-Catenin/Forkhead Box Protein O Signaling Mediates Epithelial Repair in Kidney Injury.The American journal of pathology · 2021Article
- The emerging role of EGFL6 in angiogenesis and tumor progression.International journal of medical sciences · 2020Review
- Article
- p53 upregulated by HIF-1α promotes hypoxia-induced G2/M arrest and renal fibrosis in vitro and in vivo.Journal of molecular cell biology · 2019Article
- HIF stabilization inhibits renal epithelial cell migration and is associated with cytoskeletal alterations.Scientific reports · 2018Article
- Review
- Differential Effects of EGFL6 on Tumor versus Wound Angiogenesis.Cell reports · 2017Article
- AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms.Kidney international · 2017Review
- HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells.American journal of physiology. Renal physiology · 2017Article
- Upregulation of TLR4 via PKC activation contributes to impaired wound healing in high-glucose-treated kidney proximal tubular cells.PloS one · 2017Article
- Glycogen synthase kinase 3β dictates podocyte motility and focal adhesion turnover by modulating paxillin activity: implications for the protective effect of low-dose lithium in podocytopathy.The American journal of pathology · 2014Article
- Delayed administration of a single dose of lithium promotes recovery from AKI.Journal of the American Society of Nephrology : JASN · 2014Article
- Direct phosphorylation events involved in HIF-α regulation: the role of GSK-3β.Hypoxia (Auckland, N.Z.) · 2014Review
- TGF-β1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis.Journal of the American Society of Nephrology : JASN · 2013Article
- Specific deletion of glycogen synthase kinase-3β in the renal proximal tubule protects against acute nephrotoxic injury in mice.Kidney international · 2012Article
- Exosomes Derived From Mesenchymal Stem Cells Pretreated With Ischemic Rat Heart Extracts Promote Angiogenesis via the Delivery of DMBT1.Cell transplantationArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Wound and subsequent healing are frequently associated with hypoxia. Although hypoxia induces angiogenesis for tissue remodeling during wound healing, it may also affect the healing response of parenchymal cells. Whether and how wound healing is affected by hypoxia in kidney cells and tissues is currently unknown. Here, we used scratch-wound healing and transwell migration models to examine the effect of hypoxia in cultured renal proximal tubular cells (RPTC). Wound healing and migration were significantly slower in hypoxic (1% oxygen) RPTC than normoxic (21% oxygen) cells. Hypoxia-inducible factor-1α (HIF-1α) was induced during scratch-wound healing in normoxia, and the induction was more evident in hypoxia. Nevertheless, HIF-1α-null and wild-type cells healed similarly after scratch wounding. Moreover, activation of HIF-1α with dimethyloxalylglycine in normoxic cells did not suppress wound healing, negating a major role of HIF-1α in wound healing in this model. Scratch-wound healing was also associated with glycogen synthase kinase 3β (GSK3β)/β-catenin signaling, which was further enhanced by hypoxia. Pharmacological inhibition of GSK3β resulted in β-catenin expression, accompanied by the suppression of wound healing and transwell cell migration. Ectopic expression of β-catenin in normoxic cells could also suppress wound healing, mimicking the effect of hypoxia. Conversely, inhibition of β-catenin via dominant negative mutants or short hairpin RNA improved wound healing and transwell migration in hypoxic cells. The results suggest that GSK3β/β-catenin signaling may contribute to defective wound healing in hypoxic renal cells and tissues.
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