Klf10 deficiency in mice exacerbates pulmonary inflammation by increasing expression of the proinflammatory molecule NPRA
| Autor: | Vincent H.S. Chang, Yong Tzuo Lai, Liang Ti Huang, Min Ju Wu, Hsuen Wen Chang, Winston C Y Yu, Wen Chi Wu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Transcription Genetic Neutrophils Kruppel-Like Transcription Factors Inflammation SMAD Biochemistry Proinflammatory cytokine Capillary Permeability Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Promoter Regions Genetic Regulation of gene expression biology Pneumonia Cell Biology Mice Inbred C57BL Ovalbumin 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis Early Growth Response Transcription Factors Cancer research biology.protein Tumor necrosis factor alpha medicine.symptom Receptors Atrial Natriuretic Factor Transforming growth factor |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 79:231-238 |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/j.biocel.2016.08.027 |
| Popis: | KLF10 is a transforming growth factor (TGF)-β/Smad downstream regulated gene. KLF10 binds to the promoter of target genes and mimics the effects of TGF-β as a transcriptional factor. In our laboratory, we noted that Klf10 deficiency in mice is associated with significant inflammation of the lungs. However, the precise mechanism of this association remains unknown. We previously identified NPRA as a target gene potentially regulated by KLF10 through direct binding; NPRA knockout have known that prevented lung inflammation in a mouse model of allergic asthma. Here, we further explored the regulatory association between KLF10 and NPRA on the basis of the aforementioned findings. Our results demonstrated that KLF10 acts as a transcriptional repressor of NPRA and that KLF10 binding reduces NPRA expression in vitro. Compared with wild-type mice, Klf10-deficient mice were more sensitive to lipopolysaccharide or ovalbumin challenge and showed more severe inflammatory histological changes in the lungs. Moreover, Klf10-deficient mice showed pulmonary neutrophil accumulation. These findings collectively reveal the precise site where KLF10 signaling affects pulmonary inflammation by attenuating NPRA expression. They also verify the importance of KLF10 and atrial natriuretic peptide/NPRA in exerting influences on chronic pulmonary disease pathogenesis. |
| Databáze: | OpenAIRE |
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