Xiaoping Guo1, Junming Sun1, Jinning Liang1, Siran Zhu2, Mingyuan Zhang1, Lichao Yang3, Xuejing Huang1, Kangning Xue1, Zhongxiang Mo1, Sha Wen1, Bing Hu1, Jiajuan Liu1, Yiqiang Ouyang4, Min He5,6,7. 1. Laboratory Animal Center, Guangxi Medical University, Nanning, 530021, Guangxi, China. 2. College of Animal Science and Technology, Guangxi University, Nanning, 530004, Guangxi, China. 3. School of Public Health, Guangxi Medical University, Nanning, 530021, China. 4. Laboratory Animal Center, Guangxi Medical University, Nanning, 530021, Guangxi, China. 120535001@qq.com. 5. Laboratory Animal Center, Guangxi Medical University, Nanning, 530021, Guangxi, China. hemin@gxmu.edu.cn. 6. School of Public Health, Guangxi Medical University, Nanning, 530021, China. hemin@gxmu.edu.cn. 7. Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, 530021, China. hemin@gxmu.edu.cn.
Abstract
BACKGROUND: Lung injury caused by pulmonary inflammation is one of the main manifestations of respiratory diseases. Vasorin (VASN) is a cell-surface glycoprotein encoded by the VASN gene and is expressed in the lungs of developing mouse foetuses. Previous research has revealed that VASN is associated with many diseases. However, its exact function in the lungs and the underlying mechanism remain poorly understood. METHODS AND RESULTS: To investigate the molecular mechanisms involved in lung disease caused by VASN deficiency, a VASN gene knockout (VASN-/-) model was established. The pathological changes in the lungs of VASN-/- mice were similar to those in a lung injury experimental mouse model. We further analysed the transcriptomes of the lungs of VASN-/- mice and wild-type mice. Genes in twenty-four signalling pathways were enriched in the lungs of VASN-/- mice, among which PPAR signalling pathway genes (3 genes, FABP4, Plin1, AdipoQ, were upregulated, while apoA5 was downregulated) were found to be closely related to lung injury. The most significantly changed lung injury-related gene, FABP4, was selected for further verification. The mRNA and protein levels of FABP4 were significantly increased in the lungs of VASN-/- mice, as were the mRNA and protein levels of the inflammatory factors IL-6, TNF-α and IL-1β. CONCLUSIONS: We believe that these data provide molecular evidence for the regulatory role of VASN in inflammation in the context of lung injury.
BACKGROUND: Lung injury caused by pulmonary inflammation is one of the main manifestations of respiratory diseases. Vasorin (VASN) is a cell-surface glycoprotein encoded by the VASN gene and is expressed in the lungs of developing mouse foetuses. Previous research has revealed that VASN is associated with many diseases. However, its exact function in the lungs and the underlying mechanism remain poorly understood. METHODS AND RESULTS: To investigate the molecular mechanisms involved in lung disease caused by VASN deficiency, a VASN gene knockout (VASN-/-) model was established. The pathological changes in the lungs of VASN-/- mice were similar to those in a lung injury experimental mouse model. We further analysed the transcriptomes of the lungs of VASN-/- mice and wild-type mice. Genes in twenty-four signalling pathways were enriched in the lungs of VASN-/- mice, among which PPAR signalling pathway genes (3 genes, FABP4, Plin1, AdipoQ, were upregulated, while apoA5 was downregulated) were found to be closely related to lung injury. The most significantly changed lung injury-related gene, FABP4, was selected for further verification. The mRNA and protein levels of FABP4 were significantly increased in the lungs of VASN-/- mice, as were the mRNA and protein levels of the inflammatory factors IL-6, TNF-α and IL-1β. CONCLUSIONS: We believe that these data provide molecular evidence for the regulatory role of VASN in inflammation in the context of lung injury.
Authors: Nitzan Rimon-Dahari; Lia Heinemann-Yerushalmi; Ron Hadas; Lital Kalich-Philosoph; Dafna Ketter; Nava Nevo; Dalia Galiani; Nava Dekel Journal: FASEB J Date: 2018-01-05 Impact factor: 5.191