ArticleAmerican journal of physiology. Renal physiology2013
Hypoxia-inducible factor-2α and TGF-β signaling interact to promote normoxic glomerular fibrogenesis.
Article in American journal of physiology. Renal physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 61 citations in OpenAlex.
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- Long-Term Hypoxia Upregulates Wnt and TGFβ1 Signaling in Eccrine Sweat Gland Cells In Vitro.International journal of molecular sciences · 2025Article
- Machine learning unveils hypoxia-immune gene hub for clinical stratification of thyroid-associated ophthalmopathy.Scientific reports · 2025Article
- Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment.NAR cancer · 2025Article
- Small extracellular vesicles derived from sequential stimulation of canine adipose-derived mesenchymal stem cells enhance anti-inflammatory activity.BMC veterinary research · 2025Article
- GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury.Frontiers in immunology · 2025Article
- The Role of the PAX Genes in Renal Cell Carcinoma.International journal of molecular sciences · 2024Review
- Changes of Dissociative Properties of Hemoglobin in Patients with Chronic Kidney Disease.Diagnostics (Basel, Switzerland) · 2024Article
- Mitochondrial Signaling, the Mechanisms of AKI-to-CKD Transition and Potential Treatment Targets.International journal of molecular sciences · 2024Review
- Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFβ signaling.Redox report : communications in free radical research · 2023Article
- Identification of Fibrotic Biomarkers Associated with Macrophages in Diabetic Nephropathy.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor Improves Leukocyte Energy Metabolism in Hereditary Hemorrhagic Telangiectasia.Life (Basel, Switzerland) · 2023Article
- Immunometabolism changes in fibrosis: from mechanisms to therapeutic strategies.Frontiers in pharmacology · 2023Review
- Astragaloside IV Targets Macrophages to Alleviate Renal Ischemia-Reperfusion Injury via the Crosstalk between Hif-1α and NF-κB (p65)/Smad7 Pathways.Journal of personalized medicine · 2022Article
- Altered hypoxia inducible factor regulation in hereditary haemorrhagic telangiectasia.Scientific reports · 2022Article
- SHARPIN regulates the development of clear cell renal cell carcinoma by promoting von Hippel-Lindau protein ubiquitination and degradation.Cancer science · 2021Article
- Interleukin-31 and Pruritic Skin.Journal of clinical medicine · 2021Review
- Stabilization of hypoxia-inducible factor ameliorates glomerular injury sensitization after tubulointerstitial injury.Kidney international · 2021Article
- Techniques to Assess Collagen Synthesis, Deposition, and Cross-Linking In Vitro.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Biochanin-A ameliorates pulmonary fibrosis by suppressing the TGF-β mediated EMT, myofibroblasts differentiation and collagen deposition in in vitro and in vivo systems.Phytomedicine : international journal of phytotherapy and phytopharmacology · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia-inducible factors (HIFs) are transcription factors consisting of an oxygen-sensitive α-subunit binding to a stable β-subunit. HIFs regulate multiple signaling pathways that could contribute to fibrogenesis, supporting their potential role in hypoxia-mediated renal fibrosis. We previously reported that HIF-1 is upregulated and required for transforming growth factor (TGF)-β induction of collagen in renal tubular cells. Here, we performed in vitro and in vivo studies of potential glomerular crosstalk between TGF-β and normoxic HIF signaling. HIF-α has two major isoforms, HIF-1α and HIF-2α with different target gene sets. In cultured human mesangial cells, TGF-β1 treatment increased both HIF-1α and HIF-2α expression in normoxia. TGF-β1 did not increase HIF-1α/2α mRNA levels nor decrease the rate of protein degradation, suggesting that it enhances HIF-1α/2α expression through translation. TGF-β receptor (ALK5) kinase activity was required for increased, TGF-β-stimulated HIF-α expression in response to TGF-β, and inhibiting PI3-kinase markedly decreased HIF-α expression. Blocking HIF-1α/2α expression using siRNA decreased basal and TGF-β1-stimulated type I collagen expression, while overexpressing nondegradable HIF-α increased the collagen response, with HIF-2α being significantly more effective than HIF-1α. In adriamycin-induced mouse glomerulosclerosis, HIF-2α target genes were upregulated in sclerosing glomeruli. Taken together, our data demonstrate potential signaling interaction between TGF-β and HIFs to promote renal fibrogenesis in normoxia and suggest that the HIF-2α isoform is more important during glomerulosclerosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.