Sun Meihua, Huang Yuanyuan, Li Feng, Li Haibo, Zhang Bo, Jin Lianhua
Department of Pediatrics, First Hospital, Jilin University, Changchun, jilin, 130021, China.
Department of Pediatrics, First Hospital, Jilin University, Changchun, jilin, 130021, China.
Respir Physiol Neurobiol. 2018 May;251:34-40. doi: 10.1016/j.resp.2018.02.008. Epub 2018 Feb 12.
Pro-inflammatory cytokines-induced airway remodeling was a significant feature of asthma disease. The aim of the present study was to explore the functional significance of miR-874 in tumor necrosis factor (TNF)-α-treated human fetal airway smooth muscle (fASM) cells. Here, we found that TNF-α treatment significantly down-regulated the expression of miR-874 in fASM cells. MiR-874 overexpression markedly inhibited cell viability and migration, suppressed the expression of PCNA and Ki67, reduced the expression of collagen I and collagen III, decreased the expression and activity of matrix metalloproteinase (MMP)-9 and MMP-2, and induced an obvious elevation of tissue inhibitors of metalloproteinases (TIMPs). In addition, the increased production of interleukin (IL)-6, IL-8 and eotaxin induced by TNF-α were significantly inhibited by miR-874 overexpression. Signal transducers and activators of transcription (STAT) 3 was identified as a direct target of miR-874, and STAT3 overexpression partly reversed the protective effects of miR-874 against TNF-α-induced airway remodeling. Overall, these findings demonstrate that miR-874 inhibits TNF-α-induced remodeling in human fASM cells at least in part by targeting STAT3.
促炎细胞因子诱导的气道重塑是哮喘疾病的一个显著特征。本研究的目的是探讨miR-874在肿瘤坏死因子（TNF）-α处理的人胎儿气道平滑肌（fASM）细胞中的功能意义。在此，我们发现TNF-α处理显著下调了fASM细胞中miR-874的表达。miR-874过表达显著抑制细胞活力和迁移，抑制PCNA和Ki67的表达，降低I型和III型胶原蛋白的表达，减少基质金属蛋白酶（MMP）-9和MMP-2的表达及活性，并导致金属蛋白酶组织抑制剂（TIMPs）明显升高。此外，miR-874过表达显著抑制了TNF-α诱导的白细胞介素（IL）-6、IL-8和嗜酸性粒细胞趋化因子的产生增加。信号转导和转录激活因子（STAT）3被确定为miR-874的直接靶点，STAT3过表达部分逆转了miR-874对TNF-α诱导的气道重塑的保护作用。总体而言，这些发现表明miR-874至少部分通过靶向STAT3抑制TNF-α诱导的人fASM细胞重塑。
