心肌素调节气道平滑肌细胞重塑以应对慢性哮喘损伤
2023/02/20
摘要
背景：气道平滑肌细胞的异常生长是哮喘气道重塑的关键特征之一，且与哮喘严重程度相关。哮喘中气道平滑肌细胞不适当生长的机制仍不清楚。据报道，据报道，心肌在促进胎儿肺部气道特异性平滑肌发育中起着关键的转录辅激活作用。心肌素是否控制哮喘气道平滑肌重塑还没有研究。
方法：采用卵清蛋白长时间致敏和激发的方法建立肺发育后心肌素特异性缺失的小鼠慢性哮喘模型。
结果：心肌素敲除小鼠与野生型对照小鼠的哮喘病理比较显示，抑制心肌素可减轻气道平滑肌细胞肥大和增生，并伴有气道周围炎症减轻，气道壁上纤维胶原沉积减少，气道上皮细胞中异常粘蛋白产生减弱。
结论：我们的研究表明心肌素是哮喘气道重塑的关键转录辅激活因子。抑制哮喘气道的心肌素可能是打破哮喘恶性循环的有效途径，为治疗严重和持续性哮喘提供了一种新的策略。
Myocd regulates airway smooth muscle cell remodeling in response to chronic asthmatic injury
Q. Yang, Q. Miao, H. Chen, D. Li, Y. F. Luo, J. Chiu, et al.
Abstract
BACKGROUND: Abnormal growth of airway smooth muscle cells is one of the key features in asthmatic airway remodeling, which is associated with asthma severity. The mechanisms underlying inappropriate airway smooth muscle cell growth in asthma remain largely unknown. Myocd has been reported to act as a key transcriptional coactivator in promoting airway-specific smooth muscle development in fetal lungs. Whether Myocd controls airway smooth muscle remodeling in asthma has not been investigated.
METHODS: Mice with lung mesenchyme-specific deletion of Myocd after lung development were generated, and a chronic asthma model was established by sensitizing and challenging the mice with ovalbumin for a prolonged period.
RESULTS: Comparison of the asthmatic pathology between the Myocd knockout mice and the wild-type controls revealed that abrogation of Myocd mitigated airway smooth muscle cell hypertrophy and hyperplasia, accompanied by reduced peri-airway inflammation, decreased fibrillar collagen deposition on airway walls, and attenuation of abnormal mucin production in airway epithelial cells.
CONCLUSIONS: Our study indicates that Myocd is a key transcriptional coactivator involved in asthma airway remodeling. Inhibition of Myocd in asthmatic airways may be an effective approach to breaking the vicious cycle of asthmatic progression, providing a novel strategy in treating severe and persistent asthma.
背景：气道平滑肌细胞的异常生长是哮喘气道重塑的关键特征之一，且与哮喘严重程度相关。哮喘中气道平滑肌细胞不适当生长的机制仍不清楚。据报道，据报道，心肌在促进胎儿肺部气道特异性平滑肌发育中起着关键的转录辅激活作用。心肌素是否控制哮喘气道平滑肌重塑还没有研究。
方法：采用卵清蛋白长时间致敏和激发的方法建立肺发育后心肌素特异性缺失的小鼠慢性哮喘模型。
结果：心肌素敲除小鼠与野生型对照小鼠的哮喘病理比较显示，抑制心肌素可减轻气道平滑肌细胞肥大和增生，并伴有气道周围炎症减轻，气道壁上纤维胶原沉积减少，气道上皮细胞中异常粘蛋白产生减弱。
结论：我们的研究表明心肌素是哮喘气道重塑的关键转录辅激活因子。抑制哮喘气道的心肌素可能是打破哮喘恶性循环的有效途径，为治疗严重和持续性哮喘提供了一种新的策略。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Journal of Pathology, 2023.DOI: 10.1002/path.6044）
（Journal of Pathology, 2023.DOI: 10.1002/path.6044）
Myocd regulates airway smooth muscle cell remodeling in response to chronic asthmatic injury
Q. Yang, Q. Miao, H. Chen, D. Li, Y. F. Luo, J. Chiu, et al.
Abstract
BACKGROUND: Abnormal growth of airway smooth muscle cells is one of the key features in asthmatic airway remodeling, which is associated with asthma severity. The mechanisms underlying inappropriate airway smooth muscle cell growth in asthma remain largely unknown. Myocd has been reported to act as a key transcriptional coactivator in promoting airway-specific smooth muscle development in fetal lungs. Whether Myocd controls airway smooth muscle remodeling in asthma has not been investigated.
METHODS: Mice with lung mesenchyme-specific deletion of Myocd after lung development were generated, and a chronic asthma model was established by sensitizing and challenging the mice with ovalbumin for a prolonged period.
RESULTS: Comparison of the asthmatic pathology between the Myocd knockout mice and the wild-type controls revealed that abrogation of Myocd mitigated airway smooth muscle cell hypertrophy and hyperplasia, accompanied by reduced peri-airway inflammation, decreased fibrillar collagen deposition on airway walls, and attenuation of abnormal mucin production in airway epithelial cells.
CONCLUSIONS: Our study indicates that Myocd is a key transcriptional coactivator involved in asthma airway remodeling. Inhibition of Myocd in asthmatic airways may be an effective approach to breaking the vicious cycle of asthmatic progression, providing a novel strategy in treating severe and persistent asthma.
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CCL5是哮喘中1型和2型炎症之间的潜在桥梁
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支气管哮喘气道平滑肌重塑的异质性
