Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6JAK2STAT3MMP-9 Pathway
Joint Authors
Ge, Rili
Zhu, Mingming
Yang, Min
Yang, Quanyu
Liu, Wenling
Geng, Hui
Pan, Li
Wang, Lu
Ji, Linhua
Cui, Sen
Li, Zhanquan
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-01-25
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Chronic hypoxia (CH) is characterized by long-term hypoxia that is associated with microvessel proliferation and basal membrane (BM) degradation in tissues.
The IL-6/JAK2/STAT3/MMP-9 pathway has been described in a variety of human cancers and plays an essential role in microvessel proliferation and BM degradation.
Therefore, this study investigated the role of the IL-6/JAK2/STAT3/MMP-9 pathway in hypoxia-mediated microvessel proliferation and BM degradation in the rat bone marrow.
Eighty pathogen-free Sprague Dawley male rats were randomly divided into four groups (20 per group)—control group, CH group (exposed to hypoxia in a hypobaric chamber at a simulated altitude of 5000 m for 28 d), CH + STAT3 inhibitor group (7.5 mg/kg/d), and CH + DMSO group.
Microvessel density (MVD) and BM degradation in the bone marrow were determined by immunofluorescence staining and transmission electron microscopy.
Serum IL-6 levels were assessed by enzyme-linked immunosorbent assay (ELISA), and the levels of P-JAK2, P-STAT3, and MMP-9 were assessed by western blot analysis and real-time reverse transcription PCR (RT-PCR).
Hypoxia increased serum IL-6 levels, which in turn increased JAK2 and STAT3 phosphorylation, which subsequently upregulated MMP-9.
Overexpression of MMP-9 significantly promoted the elevation of MVD and BM degradation.
Inhibition of STAT3 using an inhibitor, SH-4-54, significantly downregulated MMP-9 expression and decreased MVD and BM degradation.
Surprisingly, STAT3 inhibition also decreased serum IL-6 levels and JAK2 phosphorylation.
Our results suggest that the IL-6/JAK2/STAT3/MMP-9 pathway might be related to CH-induced microvessel proliferation and BM degradation in the bone marrow.
American Psychological Association (APA)
Zhu, Mingming& Yang, Min& Yang, Quanyu& Liu, Wenling& Geng, Hui& Pan, Li…[et al.]. 2020. Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6JAK2STAT3MMP-9 Pathway. BioMed Research International،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1138016
Modern Language Association (MLA)
Zhu, Mingming…[et al.]. Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6JAK2STAT3MMP-9 Pathway. BioMed Research International No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1138016
American Medical Association (AMA)
Zhu, Mingming& Yang, Min& Yang, Quanyu& Liu, Wenling& Geng, Hui& Pan, Li…[et al.]. Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6JAK2STAT3MMP-9 Pathway. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1138016
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1138016