Transcriptomic Evaluation of Pulmonary Fibrosis-Related Genes: Utilization of Transgenic Mice with Modifying p38 Signal in the Lungs
Autor: | Kazuya Murata, Jun-Dal Kim, Junji Ishida, Koichiro Tatsumi, Kanako Nakamura, Kana Namiki, Tatsuhiko Sudo, Masahiko Hatano, Shuichi Matsuda, Tomoyuki Kuwaki, Akiyoshi Fukamizu, Fumihiro Sugiyama, Yuji Matsuo, Yoshitoshi Kasuya |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Pulmonary compliance p38 Mitogen-Activated Protein Kinases lcsh:Chemistry Transcriptome Mice Idiopathic pulmonary fibrosis chemistry.chemical_compound 0302 clinical medicine Fibrosis Pulmonary fibrosis lcsh:QH301-705.5 Lung Spectroscopy RNA sequencing General Medicine respiratory system idiopathic pulmonary fibrosis Computer Science Applications medicine.anatomical_structure 030220 oncology & carcinogenesis Female Collagen MAP Kinase Signaling System Mice Transgenic Bleomycin Article Catalysis Inorganic Chemistry 03 medical and health sciences Immune system medicine Animals Physical and Theoretical Chemistry Molecular Biology business.industry Organic Chemistry p38 mitogen-activated protein kinase alveolar epithelial type II cells medicine.disease respiratory tract diseases Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 chemistry Alveolar Epithelial Cells Cancer research bleomycin-induced pulmonary fibrosis business |
Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 18 International Journal of Molecular Sciences, Vol 21, Iss 6746, p 6746 (2020) |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms21186746 |
Popis: | Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease that is caused by the dysregulation of alveolar epithelial type II cells (AEC II). The mechanisms involved in the progression of IPF remain incompletely understood, although the immune response accompanied by p38 mitogen-activated protein kinase (MAPK) activation may contribute to some of them. This study aimed to examine the association of p38 activity in the lungs with bleomycin (BLM)-induced pulmonary fibrosis and its transcriptomic profiling. Accordingly, we evaluated BLM-induced pulmonary fibrosis during an active fibrosis phase in three genotypes of mice carrying stepwise variations in intrinsic p38 activity in the AEC II and performed RNA sequencing of their lungs. Stepwise elevation of p38 signaling in the lungs of the three genotypes was correlated with increased severity of BLM-induced pulmonary fibrosis exhibiting reduced static compliance and higher collagen content. Transcriptome analysis of these lung samples also showed that the enhanced p38 signaling in the lungs was associated with increased transcription of the genes driving the p38 MAPK pathway and differentially expressed genes elicited by BLM, including those related to fibrosis as well as the immune system. Our findings underscore the significance of p38 MAPK in the progression of pulmonary fibrosis. |
Databáze: | OpenAIRE |
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