Decreased lymphatic HIF-2α accentuates lymphatic remodeling in lymphedema
| العنوان: | Decreased lymphatic HIF-2α accentuates lymphatic remodeling in lymphedema |
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| المؤلفون: | Stanley G. Rockson, Dongeon Kim, Wen Tian, Shravani Pasupneti, Gongyong Peng, Matthew T. Cribb, Mark R. Nicolls, Gregg L. Semenza, J. Brandon Dixon, Xinguo Jiang, Eric J. Granucci, Allen B. Tu, F. Hernan Espinoza, Yesl Kim, Amber H. Lim, Petra Dahms |
| المصدر: | J Clin Invest |
| بيانات النشر: | American Society for Clinical Investigation, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, government.form_of_government, Inflammation, Lymphatic System, Mice, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Angiopoietin-1, Basic Helix-Loop-Helix Transcription Factors, medicine, Animals, Humans, Lymphedema, Phosphorylation, Mice, Knockout, biology, business.industry, Endothelial Cells, Anatomical pathology, General Medicine, Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Receptor, TIE-2, Angiopoietin receptor, Mice, Inbred C57BL, Disease Models, Animal, Lymphatic Endothelium, 030104 developmental biology, Lymphatic system, 030220 oncology & carcinogenesis, Cancer research, government, biology.protein, Female, sense organs, medicine.symptom, business, Homeostasis, Signal Transduction, Research Article |
| الوصف: | Pathologic lymphatic remodeling in lymphedema evolves during periods of tissue inflammation and hypoxia through poorly defined processes. In human and mouse lymphedema, there is a significant increase of hypoxia inducible factor 1 α (HIF-1α), but a reduction of HIF-2α protein expression in lymphatic endothelial cells (LECs). We questioned whether dysregulated expression of these transcription factors contributes to disease pathogenesis and found that LEC-specific deletion of Hif2α exacerbated lymphedema pathology. Even without lymphatic vascular injury, the loss of LEC-specific Hif2α caused anatomic pathology and a functional decline in fetal and adult mice. These findings suggest that HIF-2α is an important mediator of lymphatic health. HIF-2α promoted protective phosphorylated TIE2 (p-TIE2) signaling in LECs, a process also replicated by upregulating TIE2 signaling through adenovirus-mediated angiopoietin-1 (Angpt1) gene therapy. Our study suggests that HIF-2α normally promotes healthy lymphatic homeostasis and raises the exciting possibility that restoring HIF-2α pathways in lymphedema could mitigate long-term pathology and disability. |
| تدمد: | 1558-8238 0021-9738 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::58fd118d1a45e1038d5b2419bfd703efTest https://doi.org/10.1172/jci136164Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....58fd118d1a45e1038d5b2419bfd703ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15588238 00219738 |
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