دورية أكاديمية

High-Altitude Hypoxia Induces Excessive Erythrocytosis in Mice via Upregulation of the Intestinal HIF2a/Iron-Metabolism Pathway

التفاصيل البيبلوغرافية
العنوان: High-Altitude Hypoxia Induces Excessive Erythrocytosis in Mice via Upregulation of the Intestinal HIF2a/Iron-Metabolism Pathway
المؤلفون: Sisi Zhou, Jun Yan, Kang Song, Ri-Li Ge
المصدر: Biomedicines, Vol 11, Iss 11, p 2992 (2023)
بيانات النشر: MDPI AG, 2023.
سنة النشر: 2023
المجموعة: LCC:Biology (General)
مصطلحات موضوعية: excessive erythrocytosis, iron metabolism, intestinal HIF2α, high-altitude hypoxia, hypoxia-inducible factor 2 alpha, Biology (General), QH301-705.5
الوصف: Excessive erythrocytosis (EE) is a preclinical form of chronic mountain sickness (CMS). The dysregulation of iron metabolism in high-altitude hypoxia may induce EE. The intestinal hypoxia-inducible factor 2 alpha (HIF2a) regulates the genes involved in iron metabolism. Considering these findings, we aimed to investigate the function and mechanism of intestinal HIF2α and the iron metabolism pathway in high-altitude EE mice. C57BL/6J mice were randomized into four groups: the low-altitude group, the high-altitude group, the high-altitude + HIF2α inhibitor group, and the high-altitude + vehicle group. In-vitro experiments were performed using the human intestinal cell line HCT116 cultured under hypoxic conditions for 24 h. Results showed that high-altitude hypoxia significantly increased the expression of intestinal HIF2α and iron metabolism-related genes, including Dmt1, Dcytb, Fpn, Tfrc, and Fth in EE mice. Genetic blockade of the intestinal HIF2α-iron metabolism pathway decreased iron availability in HCT116 cells during hypoxia. The HIF2α inhibitor PT2385 suppressed intestinal HIF2α expression, decreased iron hypermetabolism, and reduced excessive erythrocytosis in mice. These data support the hypothesis that exposure to high-altitude hypoxia can lead to iron hypermetabolism by activating intestinal HIF2α transcriptional regulation, and reduced iron availability improves EE by inhibiting intestinal HIF2α signaling.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2227-9059
Relation: https://www.mdpi.com/2227-9059/11/11/2992; https://doaj.org/toc/2227-9059
DOI: 10.3390/biomedicines11112992
URL الوصول: https://doaj.org/article/4a19803814dd4208b8a1254ce739fcce
رقم الأكسشن: edsdoj.4a19803814dd4208b8a1254ce739fcce
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:22279059
DOI:10.3390/biomedicines11112992