PRMT6 expression in lung of COPD mouse model and its relationship with inflammatory gene expression / 中国医师杂志

ABSTRACT

Objective To explore the expression of protein arginine methyltransferases 6 (PRMT6) in chronic obstructive pulmonary disease (COPD) mouse model and its correlation with inflam mation gene interleukin 6 (IL-6) and cyclooxygenase 2 (COX-2).Methods Sixteen C57BL/8J mice were randomly divided into 2 groupscontrol group and cigarette smoke extract (CSE)-induced COPD group.Each group was injected intraperitoneally with phosphate-buffered saline solutions (PBS) or CSE at days 1,12,23 and measured lung function and collected lung tissue at day 29.The morphology change of the lung tissue was determined by hematoxylin and eosin (HE) stainning.The protein expression of PRMT6,H3R2me2a and H3K4me3 were detected in lung homogenates by Western-blotting.The mRNA expression of PRMT6,IL-6 and COX-2 were measured by quantitative real-time polymerase chain reaction (qRT-PCR).Results Comparing to control group,COPD group showed typical emphysema changes in the lung tissue,and significantly decreased lung function.The mRNA and protein expression of PRMT6 in the lung tissue of the mice with COPD were significantly decreased,following with the down-regulated signal level of H3R2me2a protein expression,while the increased level of IL-6 and COX-2 mRNA.Meanwhile,PRMT6 was negatively correlated with IL-6 and COX-2 mRNA expression.Conclusions PRMT6 was significantly reduced in CSE-induced COPD mouse model,following with decreased histone H3R2 dimethylation and increased H3K4 trimethylation,negatively correlating with inflammatory gene IL-6 and COX-2 transcription expression.PRMT6 downregulation may activate the transcriptional expression of inflammatory genes involved in the development of COPD,through the regulation of histone methylation level.