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Galectin-7 overexpression destroys airway epithelial barrier in transgenic mice

Integrative Zoology 2021年第2期16卷 270-279页

作者： Jing TIAN Ruxuan HE Yimu FAN Qianqian ZHANG Baolin TIAN Chunju ZHOU Chunyan LIU Mingjing SONG Shunying ZHAO Department of Respiratory Medicine II Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Virus Laboratory Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthChina Key Laboratory of Human Disease Comparative Medicine National Health Commission of China(NHC)Beijing Engineering Research Center for Experimental Animal Models of Human DiseasesInstitute of Laboratory Animal SciencePeking Union Medicine CollegeChinese Academy of Medical SciencesBeijingChina

When the integrity of airway epithelium is destroyed,the ordered airway barrier no longer exists and increases sensitivity to viral infections and allergens,leading to the occurrence of airway inflammation such as asthma.Here,we found that galectin-7 transgenic(+)mice exhibited abnormal airway structures as embryos and after birth.These abnormalities included absent or substantially reduced pseudostratified columnar ciliated epithelium and increased monolayer cells with irregular arrangement and widening of intercellular spaces.Moreover,airway tissue from galectin-7 transgenic(+)mice showed evidence of impaired cell–cell junctions and decreased expression of zonula occludens-1(ZO-1)and E-cadherin.When treated with respiratory syncytial virus(RSV)or ovalbumin(OVA),galectin-7 transgenic(+)mice developed substantially increased bronchial epithelial detachment and apoptosis,airway smooth muscle and basement membrane thickening,and enhanced airway responsiveness.We found that Galectin-7 localized in the cytoplasm and nucleus of bronchial epithelial cells,and that increased apoptosis was mediated through mitochondrial release of cytochrome c and upregulated JNK1 activation and expression of caspase-3 in galectin-7 Tg(+)mice.These findings suggested that Galectin-7 causes airway structural defects and destroys airway epithelium barrier,which predispose the airways to RSV or OVA-induced epithelial apoptosis,injury,and other asthma responses.

关键词： airway epithelial barrier epithelial apoptosis galectin-7

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