ArticleMatrix biology : journal of the International Society for Matrix Biology2018
HIF-1α represses the expression of the angiogenesis inhibitor thrombospondin-2.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2018. 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.
- Review
- Age and Sex Impact the Role of Thrombospondin-2 and Thrombospondin-5 in Response to Hindlimb Ischemia.FASEB bioAdvances · 2026Article
- Targeting hypoxia and thrombospondin-2 in diabetic wound healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Bone-derived extracellular matrix hydrogel from thrombospondin-2 knock-out mice for bone repair.Acta biomaterialia · 2024Article
- HIF1α and HIF2α immunoreactivity in epithelial tissue of primary and recurrent pterygium by immunohistochemical analysis.International ophthalmology · 2023Article
- Current advances in nanoformulations of therapeutic agents targeting tumor microenvironment to overcome drug resistance.Cancer metastasis reviews · 2023Review
- Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2022Article
- Thrombospondin-2 holds prognostic value and is associated with metastasis and the mismatch repair process in gastric cancer.BMC cancer · 2022Article
- Is Biochemical Follow Up Possible in Peripheral Arterial Disease Treatment: Hypoxia Inducible Factor-1 Alpha?Vascular specialist international · 2021Article
- HIF-Prolyl Hydroxylase Domain Proteins (PHDs) in Cancer-Potential Targets for Anti-Tumor Therapy?Cancers · 2021Review
- Thrombospondin-2 spatiotemporal expression in skeletal fractures.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021Article
- Expression and predictive value of HIF-1α and VEGF in patients with burns following treatment.Experimental and therapeutic medicine · 2020Article
- The role of microenvironment in tumor angiogenesis.Journal of experimental & clinical cancer research : CR · 2020Review
- Cardiac fibroblast activation during myocardial infarction wound healing: Fibroblast polarization after MI.Matrix biology : journal of the International Society for Matrix Biology · 2020Review
- A simplified aortic ring assay: A usefulMatrix biology plus · 2020Article
- The role of miRNAs in the invasion and metastasis of cervical cancer.Bioscience reports · 2019Review
- Decorin is a devouring proteoglycan: Remodeling of intracellular catabolism via autophagy and mitophagy.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Hypoxia Inducible Factor 1α Inhibits the Expression of Immunosuppressive Tryptophan-2,3-Dioxygenase in Glioblastoma.Frontiers in immunology · 2019Article
- Aryl Hydrocarbon Receptor Nuclear Translocator in Vascular Smooth Muscle Cells Is Required for Optimal Peripheral Perfusion Recovery.Journal of the American Heart Association · 2018Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Thrombospondin-2 (TSP2) is a potent inhibitor of angiogenesis whose expression is dynamically regulated following injury. In the present study, it is shown that HIF-1α represses TSP2 transcription. Specifically, in vitro studies demonstrate that the prolyl hydroxylase inhibitor DMOG or hypoxia decrease TSP2 expression in fibroblasts. This effect is shown to be via a transcriptional mechanism as hypoxia does not alter TSP2 mRNA stability and this effect requires the TSP2 promoter. In addition, the documented repressive effect of nitric oxide (NO) on TSP2 is shown to be non-canonical and involves stabilization of hypoxia inducible factor-1a (HIF-1α). The regulation of TSP2 by hypoxia is supported by the in vivo observation that TSP2 has spatiotemporal expression distinct from regions of hypoxia in gastrocnemius muscle following murine hindlimb ischemia (HLI). A role for TSP2 regulation by HIF-1α is supported by the dysregulation of TSP2 expression in SM22α-cre HIF-1α KO mice following HLI. Indeed, there is a reduction in blood flow recovery in the SM22a-cre HIF-1α KO mice compared to littermate controls following HLI surgery, associated with impaired recovery and increased TSP2 levels. Moreover, SM22α-cre HIF-1α KO smooth muscle cells mice have increased TSP2 mRNA levels that persist in hypoxia. These findings identify a novel, ischemia-induced pro-angiogenic mechanism involving the transcriptional repression of TSP2 by HIF-1α.
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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.