FASEB JOURNAL
·
2024
·Vol. 38
·期 13
·e23756
·
IF 4.4
Lishen Shan,Li Chen,Wenxin Shen,Qianlan Zhou,Si Liu,Lina Han,Qinzhen Zhang,Bing Dai,Yuhong Zhao
Asthma is a chronic pulmonary disease with the worldwide prevalence. The structural alterations of airway walls, termed as “airway remodeling”, are documented as the core contributor to the airway dysfunction during chronic asthma. Forkhead box transcription factor FOXK2 is a critical regulator of glycolysis, a metabolic reprogramming pathway linked to pulmonary fibrosis. However, the role of FOXK2 in asthma waits further explored. In this study, the chronic asthmatic mice were induced via ovalbumin (OVA) sensitization and repetitive OVA challenge. FOXK2 was upregulated in the lungs of OVA mice and downregulated after adenovirus-mediated FOXK2 silencing. The lung inflammation, peribronchial collagen deposition, and glycolysis in OVA mice were obviously attenuated after FOXK2 knockdown. Besides, the expressions of FOXK2 and SIRT2 in human bronchial epithelial cells (BEAS-2B) were increasingly upregulated upon TGF-β1 stimulation and downregulated after FOXK2 knockdown. Moreover, the functional loss of FOXK2 remarkably suppressed TGF-β1-induced epithelial-mesenchymal transition (EMT) and glycolysis in BEAS-2B cells, as manifested by the altered expressions of EMT markers and glycolysis enzymes. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) inhibited the EMT in TGF-β1-induced cells, making glycolysis a driver of EMT. The binding of FOXK2 to SIRT2 was validated, and SIRT2 overexpression blocked the FOXK2 knockdown-mediated inhibition of EMT and glycolysis in TGF-β1-treated cells, which suggests that FOXK2 regulates EMT and glycolysis in TGF-β1-treated cells in a SIRT2-dependnet manner. Collectively, this study highlights the protective effect of FOXK2 knockdown on airway remodeling during chronic asthma.
研究领域:
呼吸病学
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免疫学
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分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Shanshan Jia,Pin Guo,Junhua Lu,Xujun Huang,Laming Deng,Yan Jin,Lanyan Zhao,Xiaofang Fan
Background Curcumol exhibits anti-inflammatory effect, but its effect on chronic asthma lacked research. Therefore, this study explored the role of curcumol in asthma.Methods A chronic asthmatic mice model was established by ovalbumin induction. After treatment with curcumol, airway resistance in mice was detected by forced oscillation technique. The histopathological features of airway tissues, pulmonary inflammation, and inflammation cell recruitment in the bronchoalveolar lavage fluid (BALF) of mice were detected by hematoxylin-eosin staining. Collagen deposition in the airways of mice was examined by Masson staining. The secretion of ovalbumin-IgE, IL-4, IL-5, IL-13 in mouse serum and VEGFA secretion in BALF were analyzed by ELISA. Finally, the expressions of β-catenin, Wnt5a, VEGFA, TGF-β1, Fibronectin, and MMP-9 in mice lung tissues were determined by Western blot or immunohistochemical.Results Curcumol attenuated airway hyperresponsiveness, airway remodeling, and pulmonary inflammation in chronic asthmatic mice. Curcumol relieved collagen deposition in airway tissues, inflammation cell recruitment in BALF, and reduced the up-regulation of serum ovalbumin-IgE, IL-4, IL-5, and IL-13 and BALF VEGFA in chronic asthmatic mice. In addition, curcumol attenuated the up-regulated expressions of β-catenin, Wnt5a, VEGFA, TGF-β1, Fibronectin, and MMP-9 in the lung tissues of chronic asthmatic mice, but curcumol treatment did not show such effects on healthy mice.Conclusion Our findings revealed that curcumol could ameliorate lung inflammation and airway remodeling by inhibiting the abnormal activation of the Wnt/β-catenin pathway in chronic asthmatic mice, indicating that curcumol could be used as a novel anti-asthma drug for basic and clinical research.
研究领域:
药理学
·
免疫学
·
呼吸医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）