Gang Geng1, Ying Du2, Jihong Dai1, Daiyin Tian1, Yunqiu Xia1, Zhou Fu3. 1. Department of Respiration, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. 2. Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. 3. Department of Respiration, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. Electronic address: a140122a@126.com.
Abstract
BACKGROUND: KIF3A expression was decreased in asthmatic child patients and animal. Impaired KIF3A expression resulted in increased Th2 inflammation in mice and apoptosis in renal tubular epithelium and photoreceptor cells. This work aimed to investigate the role of KIF3A in epithelium apoptosis and bronchial inflammation in asthma. METHODS: After establishment of ovalbumin induced asthma, the mice were infected with KIF3A adenovirus through nasal cavity inhalation. KIF3A expression and apoptosis in epithelia of nasal mucosa and bronchia were determined using qRT-PCR, western blotting, immunohistochemistry and TUNEL staining. The mRNA expression of COX-2, IL-4, IL-5, IL-13, IL-6, IL-10 and TNF-α was also measured. In vitro, human bronchial epithelial cell line 16HBE 14o- was stimulated with IL-4, IL-13 and TNF-α, accompanied by KIF3A knockdown or overexpression using siRNA or KIF3A adenovirus respectively. Apoptosis, mRNA expression of CCL17, CCL26, IL-5 and IL-8, and protein expression of COX-2 and β-catenin were determined using flow cytometry, qRT-PCR and western blotting. RESULTS: KIF3A expression was reduced in epithelia of nasal mucosa and bronchia of asthmatic mice, and overexpression of KIF3A ameliorated epithelial cell apoptosis and bronchial inflammation in asthmatic mice. In vitro, KIF3A knockdown significantly promoted epithelium apoptosis, facilitated the transcription of CCL17, CCL26, IL-5 and IL-8, and increased the protein levels of COX-2 and β-catenin translocation, whereas overexpression of KIF3A exhibited the opposite effect. CONCLUSION: KIF3A plays an important role in epithelium apoptosis and bronchial inflammation in asthma, and may be a potential target for asthma treatment.
BACKGROUND:KIF3A expression was decreased in asthmatic childpatients and animal. Impaired KIF3A expression resulted in increased Th2inflammation in mice and apoptosis in renal tubular epithelium and photoreceptor cells. This work aimed to investigate the role of KIF3A in epithelium apoptosis and bronchial inflammation in asthma. METHODS: After establishment of ovalbumin induced asthma, the mice were infected with KIF3A adenovirus through nasal cavity inhalation. KIF3A expression and apoptosis in epithelia of nasal mucosa and bronchia were determined using qRT-PCR, western blotting, immunohistochemistry and TUNEL staining. The mRNA expression of COX-2, IL-4, IL-5, IL-13, IL-6, IL-10 and TNF-α was also measured. In vitro, human bronchial epithelial cell line 16HBE 14o- was stimulated with IL-4, IL-13 and TNF-α, accompanied by KIF3A knockdown or overexpression using siRNA or KIF3A adenovirus respectively. Apoptosis, mRNA expression of CCL17, CCL26, IL-5 and IL-8, and protein expression of COX-2 and β-catenin were determined using flow cytometry, qRT-PCR and western blotting. RESULTS:KIF3A expression was reduced in epithelia of nasal mucosa and bronchia of asthmatic mice, and overexpression of KIF3A ameliorated epithelial cell apoptosis and bronchial inflammation in asthmatic mice. In vitro, KIF3A knockdown significantly promoted epithelium apoptosis, facilitated the transcription of CCL17, CCL26, IL-5 and IL-8, and increased the protein levels of COX-2 and β-catenin translocation, whereas overexpression of KIF3A exhibited the opposite effect. CONCLUSION:KIF3A plays an important role in epithelium apoptosis and bronchial inflammation in asthma, and may be a potential target for asthma treatment.
Authors: Mariana L Stevens; Zhonghua Zhang; Elisabet Johansson; Samriddha Ray; Amrita Jagpal; Brandy P Ruff; Arjun Kothari; Hua He; Lisa J Martin; Hong Ji; Kathryn Wikenheiser-Brokamp; Matthew T Weirauch; Dorothy M Supp; Jocelyn M Biagini Myers; Gurjit K Khurana Hershey Journal: Nat Commun Date: 2020-08-14 Impact factor: 14.919
Authors: Irene H Heijink; Virinchi N S Kuchibhotla; Mirjam P Roffel; Tania Maes; Darryl A Knight; Ian Sayers; Martijn C Nawijn Journal: Allergy Date: 2020-06-16 Impact factor: 13.146