Anti-inflammatory effects of miRNA-146a induced in adipose and periodontal tissues
Anti-inflammatory effects of miRNA-146a induced in adipose and periodontal tissues
复制标题
DOI：
10.1016/j.bbrep.2020.100757
复制
发表时间：
2020-07-01
影响因子：
2.7
通讯作者：
Nishimura, Fusanori
中科院分区：
文献类型：
--
作者：
Sanada, Taiki;Sano, Tomomi;Nishimura, Fusanori
microRNA（miRNA）在炎症反应、分化增殖、肿瘤发生等多种细胞生物学过程中发挥重要作用。miR-146 a被认为是炎症反应的负调节因子。尽管已经报道其在发炎的脂肪和牙周组织中表达，但是，miR-146 a对这两种组织中的炎症反应的抑制作用还没有很好地理解。因此，在本研究中，研究了miR-146 a对脂肪和牙周炎症的抑制作用。体外研究表明，与转染的对照miRNA相比，miR-146 a转染到脂肪细胞或牙龈成纤维细胞中导致细胞因子基因表达降低，在脂多糖（LPS）存在下将细胞与巨噬细胞共培养时观察到。类似地，miR-146 a转染到巨噬细胞中导致响应于LPS刺激的TNF-α基因和蛋白质的表达降低。体内研究显示，通过尾静脉连续静脉注射miR-146 a至小鼠中，保护小鼠免于发展高脂饮食诱导的肥胖，并且脂肪和牙周组织中的炎性细胞因子基因表达下调。miR-146 a似乎通过负反馈机制由巨噬细胞源性炎症信号如TNF-α诱导，并且其抑制脂肪和牙周组织中的炎症反应。因此，miR-146 a可能被认为是一种潜在的治疗分子，并作为一种常见的炎症调节剂，肥胖诱导的糖尿病和相关的牙周疾病。
MicroRNA (miRNA) plays an important role in diverse cellular biological processes such as inflammatory response, differentiation and proliferation, and carcinogenesis. miR-146a has been suggested as a negative regulator of the inflammatory reaction. Although, it has been reported as expressed in inflamed adipose and periodontal tissues, however, miR-146a's inhibitory effects against inflammatory response in both the tissues, are not well understood. Therefore, in this study, the inhibitory effects of miR-146a on both adipose and periodontal inflammation, was investigated. In vitro study has revealed that miR-146a transfection into either adipocytes or gingival fibroblasts, has resulted in a reduced cytokine gene expression, observed on co-culturing the cells with macrophages in the presence of lipopolysaccharides (LPS), in comparison to the control miRNA transfected. Similarly, miR-146a transfection into macrophages resulted in a reduced expression of TNF-alpha gene and protein in response to LPS stimulation. In vivo study revealed that a continuous intravenous miR-146a administration into mice via tail vein, protected the mice from developing high-fat diet-induced obesity and the inflammatory cytokine gene expression was down-regulated in both adipose and periodontal tissues. miR-146a appeared to be induced by macrophage-derived inflammatory signals such as TNF-alpha by negative feed-back mechanism, and it suppressed inflammatory reaction in both adipose and periodontal tissues. Therefore, miR-146a could be suggested as a potential therapeutic molecule and as a common inflammatory regulator for both obesity-induced diabetes and related periodontal diseases.