Clinical immunology (Orlando, Fla.) · 2023
Increased CYR61 expression activates CCND1/c-Myc pathway to promote nasal epithelial cells proliferation in chronic rhinosinusitis with nasal polyps.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Luo Chunyu, Zhu Ying, Zhou Jiayao, Sun Xiwen, Zhang Shiyao, Tan Shaolin, Li Zhipeng, Lin Hai, Zhang Weitian
Аннотация
PURPOSE: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a chronic sinonasal inflammatory disease characterized histologically by hyperplastic nasal epithelium and epithelial cells proliferation. Cysteine-rich angiogenic inducer 61 (CYR61) acts as a positive regulator of cell cycle process. Cyclin D1 (CCND1) and c-Myc play key roles in the processes of cell cycle and cell growth. The purpose of our research was to explore the expression and roles of CYR61, CCND1 and c-Myc in CRSwNP.
METHODS: FeaturePlot and vlnPlot functions embedded in the seurat package (version 4.1.1) of R software (version 4.2.0) were applied to explore the cellular distribution of CYR61, CCND1 and c-Myc in the single-cell RNA sequencing (scRNA-seq) dataset of nasal tissue samples. CYR61, CCND1 and c-Myc immunolabeling and mRNA levels in nasal tissue samples were assessed by immunohistochemistry and real-time PCR. Co-localization of CYR61, CCND1 and c-Myc with basal epithelial cell marker P63 was assayed using double-label immunofluorescence staining. Furthermore, we collected and cultured human nasal epithelial cells (HNEC) to assess the regulation and role of CYR61 in vitro study.
RESULTS: CYR61, CCND1 and c-Myc were primarily expressed by nasal epithelial cells. Significant upregulation of CYR61, CCND1 and c-Myc positive cells and increased levels of CYR61, CCND1 and c-Myc mRNA were found in nasal polyps in comparison to control samples. Of note, CYR61 mRNA and protein levels were altered by SEB, LPS, IFN-γ, IL-13, IL-17A and TGF-β1 in HNEC. In addition, CYR61 intervention could increase CCND1 and c-Myc mRNA and protein levels to promote HNEC proliferation, and siRNA against ITGA2 (si-ITGA2) could reverse CYR61 induced upregulation of CCND1 and c-Myc mRNA and protein levels in HNEC and cell proliferation of HNEC.
CONCLUSIONS: CYR61, CCND1 and c-Myc were primarily expressed by epithelial cells in nasal mucosa. CYR61, CCND1 and c-Myc expression levels were increased in CRSwNP compared with controls. CYR61 could interact with ITGA2 to enhance HNEC proliferation via upregulating CCND1 and c-Myc levels in the HNEC, leading to hyperplastic nasal epithelium in CRSwNP.
METHODS: FeaturePlot and vlnPlot functions embedded in the seurat package (version 4.1.1) of R software (version 4.2.0) were applied to explore the cellular distribution of CYR61, CCND1 and c-Myc in the single-cell RNA sequencing (scRNA-seq) dataset of nasal tissue samples. CYR61, CCND1 and c-Myc immunolabeling and mRNA levels in nasal tissue samples were assessed by immunohistochemistry and real-time PCR. Co-localization of CYR61, CCND1 and c-Myc with basal epithelial cell marker P63 was assayed using double-label immunofluorescence staining. Furthermore, we collected and cultured human nasal epithelial cells (HNEC) to assess the regulation and role of CYR61 in vitro study.
RESULTS: CYR61, CCND1 and c-Myc were primarily expressed by nasal epithelial cells. Significant upregulation of CYR61, CCND1 and c-Myc positive cells and increased levels of CYR61, CCND1 and c-Myc mRNA were found in nasal polyps in comparison to control samples. Of note, CYR61 mRNA and protein levels were altered by SEB, LPS, IFN-γ, IL-13, IL-17A and TGF-β1 in HNEC. In addition, CYR61 intervention could increase CCND1 and c-Myc mRNA and protein levels to promote HNEC proliferation, and siRNA against ITGA2 (si-ITGA2) could reverse CYR61 induced upregulation of CCND1 and c-Myc mRNA and protein levels in HNEC and cell proliferation of HNEC.
CONCLUSIONS: CYR61, CCND1 and c-Myc were primarily expressed by epithelial cells in nasal mucosa. CYR61, CCND1 and c-Myc expression levels were increased in CRSwNP compared with controls. CYR61 could interact with ITGA2 to enhance HNEC proliferation via upregulating CCND1 and c-Myc levels in the HNEC, leading to hyperplastic nasal epithelium in CRSwNP.