Overexpression of hypoxia-inducible factor 1α is associated with neutrophilic inflammation in chronic rhinosinusitis with nasal polyps

Yu, Ziming; Wang, Yu; Hu, Xianting; Xu, Haitian; Han, Miaomiao; Zhang, Jia; Wen, Wang; Shu, Hai-Rong; Li, Hua-Bin

doi:10.1016/j.anl.2019.09.011

Cited by 10 publications

(27 citation statements)

References 25 publications

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“…Subsequently, we examined the downstream target of XBP1.The levels of HIF-1a in relatively low eosinophilic infiltration tissue samples were higher than those in control and eosinophilic CRSwNP samples [ 24 ], and HIF-1a is related to neutrophilic inflammation and glucocorticoid resistance in CRSwNP patients [ 25 ]. Moreover, Khalil et al evidenced that whole tissue from CRSwNP subjects showed promoted HIF-1a gene expression [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

XBP1 Regulates the Transcription of HIF-1a in BALB/c Mice with Chronic Rhinosinusitis without Polyps

Meng

2022

Analytical Cellular Pathology

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X-box binding protein 1 (XBP1) is a transcription factor that recognizes the CRE-like element in enhancers of human T-cell leukemia virus and MHC class II gene and induces their transcription. This study was performed to characterize the function of XBP1, which was identified to be a differentially expressed gene via GEO database, in chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP). XBP1 expression was significantly elevated in both CRSsNP patients and mice who were accompanied with mucosal thickening, goblet cell hyperplasia and chemosis, glandular hyperplasia, and dense infiltration of inflammatory cells. Silencing of XBP1 suppressed the development of CRSsNP in mice. Mechanistically, knockdown of XBP1 downregulated the expression of hypoxia-inducible factor 1-alpha (HIF-1a), and overexpression of XBP1 led to the opposite result. Silencing of HIF-1a inhibited β-catenin expression and impaired the Wnt/β-catenin pathway. Further overexpression of HIF-1a in XBP1-silenced CRSsNP mice exacerbated pathological changes in mouse nasal mucosal tissues, promoted inflammation, and activated the Wnt/β-catenin pathway. Taken together, overexpression of XBP1 may be associated with increased expression of HIF-1a and possibly contribute to the Wnt/β-catenin pathway activation and the development of CRSsNP.

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Section: Discussionmentioning

confidence: 99%

XBP1 Regulates the Transcription of HIF-1a in BALB/c Mice with Chronic Rhinosinusitis without Polyps

Meng

2022

Analytical Cellular Pathology

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“…It is worthy of note that HIF-1α is closely associated with disease severity in knee osteoarthritis [ 18 ]. HIF-1α is significantly increased in polyp tissues, which promotes neutrophilic inflammation in chronic rhinosinusitis with nasal polyps patients [ 19 ]. Importantly, agent that inhibits HIF-1α-induced inflammation and apoptosis in macrophages can be used for the treatment of atherosclerosis [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible transcription factor-1α inhibition by topotecan protects against lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes

Zhang

Zhou

et al. 2021

BioMed Eng OnLine

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Background Myocarditis, an inflammatory disease of the myocardium, is a serious hazard to human life due to the expansion of inflammatory lesions in the myocardium. The aim of this study was to investigate the role of hypoxia-inducible transcription factor (HIF)-1α and its inhibitor topotecan in the pathogenesis of myocarditis. Methods H9c2 cardiomyoblasts was stimulated with lipopolysaccharide (LPS) to simulate myocarditis model in vitro. The levels of myocardial damage markers were determined using commercially available kits. Western blotting was used to evaluate HIF-1α expression after LPS challenge. Then, after HIF-1α silencing, the contents of inflammatory factors were determined with enzyme-linked immunosorbent assay (ELISA). Cell viability was tested by means of a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed by flow cytometry, and the expression of apoptotic proteins was examined using western blot analysis. Subsequently, HIF-1α was overexpressed and topotecan was employed to treat H9c2 cells under LPS exposure condition. The biological functions were detected again. Results LPS significantly elevated the levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I) in supernatant of H9c2 cell lysates. Additionally, LPS led to the notably upregulated expression of HIF-1α. HIF-1α-knockdown markedly decreased the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 compared with the LPS-induced group. Moreover, the cell viability was conspicuously enhanced and cell apoptotic ratio was remarkably reduced, accompanied by downregulated expression of Bax, Bim, caspase 3 and caspase 9 after HIF-1α silencing. Consistently, HIF-1α gain-of-function significantly promoted the production of inflammatory cytokines and cell apoptosis, which was partially counteracted by topotecan administration. Conclusion To conclude, these findings demonstrated that HIF-1α inhibition by topotecan ameliorates LPS-induced myocarditis in vitro, providing a new approach in the treatment of myocarditis.

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“…In previous studies discussing the effects of obstructive sleep apnea (OSA) on glaucoma, including a population-based study conducted in the same region as the current study, patients with OSA showed a greater chance to develop and aggravate glaucoma [23,24,25,26]. The CRS is also characterized by respiratory disturbance and hypoxia due to the nasal ostial obstructions [27,28], and the hypoxia-related mediators including hypoxia-inducible factor 1 α and high-mobility group box 1 would be elevated in patient with CRS and lead to further inflammation process [29,30]. Moreover, the severe hypoxia featured with elevated heat shock protein 70 was associated with worse surgical outcome of FESS, which may let the inflammatory as well as the hypoxic damage of CRS persist [31].…”

Section: Discussionmentioning

confidence: 99%

The Development of Glaucoma after Surgery-Indicated Chronic Rhinosinusitis: A Population-Based Cohort Study

Chau

Sun

et al. 2019

IJERPH

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This study investigates the development of glaucoma in subjects with surgery-indicated chronic rhinosinusitis (CRS) by the use of the National Health Insurance Research Database in Taiwan. Individuals that received the functional endoscopic sinus surgery (FESS) with a diagnostic code of CRS were regarded as surgery-indicated CRS and enrolled in the study group. Four non-CRS patients were age- and gender-matched to each patient in the study group. The exclusion criteria included legal blindness, ocular tumor, history of eyeball removal, and previous glaucoma. The outcome was regarded as the development of glaucoma, and conditional logistic regression was used for the statistical analysis, which involved multiple potential risk factors in the multivariate model. A total of 6506 patients with surgery-indicated CRS that received FESS and another 26,024 non-CRS individuals were enrolled after exclusion. The age and gender distributions were identical between the two groups due to matching. There were 108 and 294 glaucoma events in the study group and control group, respectively, during the follow-up period, and the study group had a significantly higher adjusted hazard ratio (1.291, 95% confidential interval: 1.031–1.615). The cumulative probability analysis also revealed a correlation between the occurrence of glaucoma and the CRS disease interval. In the subgroup analysis, the chance of developing open-angle glaucoma and normal-tension glaucoma was significantly higher in the study group than in the control group. In conclusion, the existence of surgery-indicated CRS is a significant risk factor for the development of glaucoma, which correlated with the disease interval.

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Overexpression of hypoxia-inducible factor 1α is associated with neutrophilic inflammation in chronic rhinosinusitis with nasal polyps

Cited by 10 publications

References 25 publications

XBP1 Regulates the Transcription of HIF-1a in BALB/c Mice with Chronic Rhinosinusitis without Polyps

XBP1 Regulates the Transcription of HIF-1a in BALB/c Mice with Chronic Rhinosinusitis without Polyps

Hypoxia-inducible transcription factor-1α inhibition by topotecan protects against lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes

The Development of Glaucoma after Surgery-Indicated Chronic Rhinosinusitis: A Population-Based Cohort Study

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