3.HIF-1: structure, biology and natural modulators.
Chao YANG ; Zhang-Feng ZHONG ; Sheng-Peng WANG ; Chi-Teng VONG ; Bin YU ; Yi-Tao WANG
Chinese Journal of Natural Medicines (English Ed.) 2021;19(7):521-527
Hypoxia-inducible factor 1 (HIF-1), as a main transcriptional regulator of metabolic adaptation to changes in the oxygen environment, participates in many physiological and pathological processes in the body, and is closely related to the pathogenesis of many diseases. This review outlines the mechanisms of HIF-1 activation, its signaling pathways, natural inhibitors, and its roles in diseases. This article can provide new insights in the diagnosis and treatment of human diseases, and recent progress on the development of HIF-1 inhibitors.
Disease
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Humans
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Hypoxia-Inducible Factor 1/physiology*
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Oxygen
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Signal Transduction
4.Advances on hypoxia inducible factor-1.
Chinese Medical Journal 2013;126(18):3567-3571
5.HIF-1 signal pathway in cellular response to hypoxia.
Ping-ping WANG ; Fan-ping KONG ; Xue-qun CHEN ; Ji-zeng DU
Journal of Zhejiang University. Medical sciences 2011;40(5):559-566
HIF-1 is composed of HIF-1α and HIF-1β subunits. It promotes target genes transcription under hypoxia and plays essential roles in cell development, physiological adaptations, and pathological processes. In the past 10 years, the research on signaling pathways of HIF-1 in response to cell hypoxia stress, especially on HIF-1α-mediated gene transcription has made great progress.
Animals
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Cell Hypoxia
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physiology
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Humans
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Hypoxia-Inducible Factor 1
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metabolism
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Signal Transduction
6.Research progress of mechanism of hypoxia-inducible factor-1α signaling pathway in condylar cartilage growth and remodeling.
West China Journal of Stomatology 2016;34(6):639-642
The condylar cartilage was adapted to hypoxic conditions in vivo. However, condylar cartilage cells exposed in normoxia in vitro affect the chondrocyte phenotype and cartilage matrix formation. This condition also resulted in great difficulty in chondrocyte research. Culturing chondrocyte should be simulated in in vivo hypoxia environment as much as possible. The hypoxia-inducible factor-1α (HIF-1α) demonstrates an important transcription factor of adaptive response to hypoxic conditions. HIF-1α also plays an active role in maintaining homeostasis and function of chondrocytes. This review summarized current knowledge of the HIF-1α structure, signaling pathway, and mechanism of HIF-1α in the condylar cartilage repair.
Cartilage
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Chondrocytes
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Humans
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Hypoxia
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Hypoxia-Inducible Factor 1, alpha Subunit
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Signal Transduction
7.Airway epithelial cells increase macrophage chemotaxis and inflammatory cytokine secretion under hypoxic conditions.
Xingwu CHEN ; Lilong QING ; Zhengui SUN ; Min XING ; Leilei ZANG ; Hanli WANG
Journal of Central South University(Medical Sciences) 2019;44(2):134-143
To investigate the effects of airway epithelial cells on macrophages chemotaxis and inflammatory cytokine expression under hypoxic conditions.
Methods: Human bronchial epithelial cells (HBE) treated with different concentrations (0, 100, 200, 400, 800 μmol/L) of CoCl2 or transfected with HIF-1α siRNA were co-cultured with THP-1-derived M1 macrophages or M2 macrophages. The chemotactic effects on macrophages were analyzed by Transwell assay. The levels of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were detected by ELISA, and HIF-1α or Cav-1 mRNA expression in HBE or macrophages was detected by RT-qPCR.
Results: HBE cells promoted macrophages chemotaxis in a time- and concentration-dependent manner. Compared to un-transfected group, the chemotactic ability of HBE transfected with HIF-1α siRNA was significantly weakened (P<0.01). Under the same culture conditions, the chemotaxis of M2 macrophages was greater than that in THP1-derived M1 macrophages. The concentrations of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were increased in a time-and concentration-dependent manner. The concentrations of TNF-α and IFN-γ were increased further after co-culturing for 8 and 12 h; while IL-4, IL-13 and IL-10 concentrations were increased further during 24 h of co-culture. The levels of cytokines in the supernatants of macrophages co-cultured with HBE and transfected with HIF-1α siRNA were significantly lower than those in un-transfected cells (P<0.05 or P<0.01). The reduction of TNF-α or IFN-γ was more obvious. The expression of HIF-1α or Cav-1 mRNA in HBE or macrophages was increased in a concentration-dependent manner after 8 or 12 h co-culture, which was significantly reduced when HBE was transfected with HIF-1α siRNA.
Conclusion: Airway epithelial cells can enhance macrophages chemotaxis and pro-inflammatory cytokines expressions under hypoxic condition. HIF-1α and Cav-1 may be the important mediators in these processes.
Cell Hypoxia
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Chemotaxis
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Cytokines
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Epithelial Cells
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit
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Macrophages
8.Expression and significance of jumonji domain-containing protein 2B and hypoxia inducible factor-1α in non-Hodgkin lymphoma tissues in children.
Yu-Qiao DIAO ; Jian WANG ; Xiu-Li ZHU ; Jian CHEN ; Yu ZHENG ; Lian JIANG ; Yue-Ping LIU ; Ruo-Heng DAI ; Yi-Wei YAN
Chinese Journal of Contemporary Pediatrics 2023;25(11):1150-1155
OBJECTIVES:
To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children.
METHODS:
Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed.
RESULTS:
The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (rs=0.333, P=0.024).
CONCLUSIONS
JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.
Humans
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Child
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Hypoxia-Inducible Factor 1, alpha Subunit
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Prognosis
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Hypoxia
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Lymphoma, Non-Hodgkin
10.Research progress of hypoxia-inducible factor 1 inhibitors against tumors.
Fei NIU ; Yan LI ; Fang-Fang LAI ; Xiao-Guang CHEN
Acta Pharmaceutica Sinica 2014;49(6):832-836
Hypoxia occurs in chronic and acute vascular diseases and tumor formation. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducible factor 1 (HIF-1). Tumor hypoxia mediated by HIF-1 would facilitate the likelihood of resistance to chemotherapy and radiotherapy, proliferation, metastasis and the invasive potential; all of which culminate in a decrease in patient survival. And HIF-1 alpha subunit decides the activity of HIF-1, which is regulated by oxygen. So understanding the role of HIF in signal pathway, drug resistance mechanism and its feature is crucial for developing novel anticancer therapies. In recent years, more attentions have focused on HIF-1 alpha inhibitors. It is expected that development of more potent and selective HIF inhibitors will provide an effective treatment of cancer and other HIF-related diseases. So we will focus on the biological characteristics and mechanism of HIF-1 to review currently studied HIF-1 inhibitors.
Cell Death
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Humans
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Hypoxia-Inducible Factor 1
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antagonists & inhibitors
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metabolism
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Hypoxia-Inducible Factor 1, alpha Subunit
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antagonists & inhibitors
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metabolism
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Neoplasms
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drug therapy
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Oxygen
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metabolism
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Signal Transduction