Lnc01287/miR-4500通过TGF-β/Smad通路影响特发性肺纤维化进展的相关机制  

Related mechanisms of effect of Lnc01287/miR-4500 on progression of idiopathic pulmonary fibrosis via transforming growth factor-β/Smad signaling

作　　者：薛成 林益华[1] 史永红[1] Xue Cheng;Lin Yihua;Shi Yonghong(Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital of Xiamen University,Xiamen 361000,China)

机构地区：[1]厦门大学附属第一医院呼吸与危重症医学科,361000

出　　处：《国际呼吸杂志》2021年第9期641-654,共14页International Journal of Respiration

摘　　要：目的探索Lnc01287/miR-4500通过转化生长因子β(TGF-β)/Smad通路影响特发性肺纤维化进展的相关机制。方法首先原代培养人肺成纤维细胞与人肺瘢痕成纤维细胞,检测Lnc01287、miR-4500、TGF-β/Smad通路在2种细胞中的表达;再通过在线生物信息学网站与双荧光素酶报告基因实验,研究Lnc01287、miR-4500、TGF-β/Smad通路间的相互作用关系;最后通过基因过表达与抑制技术,研究Lnc01287/miR-4500通过TGF-β/Smad通路对人肺瘢痕成纤维细胞增殖的调控。结果在人肺瘢痕成纤维细胞中,Lnc01287、TGF-β/Smad通路是高表达的,而miR-4500是低表达的。Lnc01287通过靶向抑制miR-4500,然后被抑制的miR-4500通过靶向激活TGF-β/Smad通路,最终促进人肺瘢痕成纤维细胞的生长。结论 Lnc01287是治疗特发性肺纤维化的有希望的靶点,可针对此靶点开发药物,减缓特发性肺纤维化的进展。Objective To explore related mechanisms of effect of Lnc01287/miR-4500 on the progression of idiopathic pulmonary fibrosis via transforming growth factor-β(TGF-β)/Smad signaling.Methods Firstly,primary human lung fibroblasts and primary human lung hypertrophic scar fibroblasts were cultured,the expressions of Lnc01287,miR-4500,and TGF-β/Smad signaling between these two cells were compared.Secondly,the relationship among Lnc01287,miR-4500,and TGF-β/Smad signaling was studied via online bioinformatics websites and dual-luciferase reporter assay.Thirdly,how Lnc01287/miR-4500 affects the proliferation of primary human lung hypertrophic scar fibroblasts via TGF-β/Smad signaling was studied by using gene overexpression and suppression techniques.Results Lnc01287 and TGF-β/Smad signaling were upregulated and miR-4500 was downregulated in primary human lung hypertrophic scar fibroblasts.Lnc01287 targeted miR-4500 to inhibit its expression,then miR-4500 suppression targeted TGF-β/Smad signaling to activate it,and finally the proliferation of primary human lung hypertrophic scar fibroblasts was promoted.Conclusions Lnc01287 is a promising target to treat idiopathic pulmonary fibrosis.The new drugs that target this molecule can be developed and slow the progression of this disease.

关 键 词：特发性肺纤维化 Lnc01287 miR-4500 SMAD3 

分 类 号：R563[医药卫生—呼吸系统]