Effect of low VEGF on lung development and function
| Autor: | May Zun Zaw Myint, Noor Bahadar, Luqing Zhang, Hsu Htoo, Yang Chen, Farooq Hayel, Fatoumata Binta Bah, Zin Mar Oo, Yaowu Zheng, Salah Adlat, Rajiv Kumar Sah, Xuechao Feng, Jia Jia, Mi Kaythi Chan |
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| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
0301 basic medicine Genetically modified mouse Untranslated region Lung Alveolar septum respiratory system Biology 01 natural sciences Molecular medicine Pathogenesis Vascular endothelial growth factor 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology medicine.anatomical_structure chemistry Gene expression Genetics medicine Cancer research Animal Science and Zoology Agronomy and Crop Science 010606 plant biology & botany Biotechnology |
| Zdroj: | Transgenic Research. 30:35-50 |
| ISSN: | 1573-9368 0962-8819 |
| DOI: | 10.1007/s11248-020-00223-w |
| Popis: | Vascular endothelial growth factor (VEGF) is important for lung development and function but ideal mouse models are limited to decipher the quantitative relationship between VEGF expression levels and its proper development and pathogenesis. Human SPC promoter has been used to faithfully express genes or cDNAs in the pulmonary epithelium in many transgenic mouse models. In the study, a mouse model of lung-specific and reversible VEGF repression (hspc-rtTRtg/+/VegftetO/tetO) was generated. Human SPC promoter was used to drive lung-specific rtTR expression, a cDNA coding for doxycycline-regulated transcription repression protein. By crossing with VegftetO/tetO mice, that has tetracycline operator sequences insertion in 5'-UTR region, it allows us to reversibly inhibit lung VEGF transcription from its endogenous level through doxycycline food, water or injection. The tissue-specific inhibition of VEGF is used to mimic abnormal expression levels of VEGF in lung. Reduced VEGF expression in lung is confirmed by quantitative real time PCR and immunoblotting. Lung development and structure was analyzed by histology analysis and found significantly affected under low VEGF. The pulmonary epithelium and alveolarization are found abnormal with swelling alveolar septum and enlargement of air space. Genome-wide gene expression analysis identified that immune activities are involved in the VEGF-regulated lung functions. The transgenic mouse model can be used to mimic human pulmonary diseases. The mouse model confirms the important regulatory roles of epithelial expressed VEGF in lung development and function. This mouse model is valuable for studying VEGF-regulated lung development, pathogenesis and drug screening under low VEGF expression. |
| Databáze: | OpenAIRE |
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