Pediatric Intensive Care Unit, The Second People's Hospital of Liaocheng, Affiliated to Shandong First Medical University, Linqing, Shandong 252600, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12019. Epub 2021 Mar 24.
pneumonia (MPP) is a type of pneumonia induced by (MP) infection. The present study investigated the effect of long non‑coding RNA growth arrest‑specific 5 (GAS5) in MPP and the underlying molecular mechanism of this. The expression of GAS5, microRNA‑222‑3p, (miR‑222‑3p) and tissue inhibitor of metalloproteinases‑3 (TIMP3) in MPP was investigated using reverse transcription‑quantitative PCR. Lipid‑associated membrane protein (LAMP)‑induced THP‑1 cells were used to model MPP. The viability of LAMP‑induced THP‑1 cells was analyzed using an MTT assay. Expression levels of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α (TNF‑α) pro‑inflammatory cytokines, and the anti‑inflammatory cytokine heme oxygenase‑1 (HO‑1) in LAMP‑induced THP‑1 cells were measured by ELISA. A dual‑luciferase reporter assay assessed the associations among GAS5, miR‑222‑3p and TIMP3. The expression of GAS5 and TIMP3 was downregulated in MPP. Expression of miR‑222‑3p was upregulated. GAS5‑overexpression increased the viability of LAMP‑induced THP‑1 cells. GAS5 upregulation decreased the levels of IL‑1β, IL‑6, TNF‑α and HO‑1 levels in LAMP‑induced THP‑1 cells. GAS5 directly interacted with miR‑222‑3p. TIMP3 was a target of miR‑222‑3p. miR‑222‑3p upregulation or TIMP3‑knockdown reversed the promotion effect on cell viability as well as the inhibitory effect on inflammation caused by GAS5‑overexpression in LAMP‑induced THP‑1 cells. GAS5‑overexpression increased the viability and decreased the inflammation of LAMP‑induced THP‑1 cells by regulating the miR‑222‑3p/TIMP3 axis. These results demonstrated a potential therapeutic target for MPP treatment.
肺炎支原体肺炎（MPP）是由肺炎支原体（MP）感染引起的肺炎类型。本研究探讨了长非编码 RNA 生长停滞特异性 5（GAS5）在 MPP 中的作用及其潜在的分子机制。采用逆转录定量 PCR 检测 MPP 中 GAS5、微小 RNA-222-3p（miR-222-3p）和组织金属蛋白酶抑制剂 3（TIMP3）的表达。采用脂相关膜蛋白（LAMP）诱导 THP-1 细胞建立 MPP 模型。采用 MTT 法分析 LAMP 诱导的 THP-1 细胞活力。采用 ELISA 法检测 LAMP 诱导的 THP-1 细胞中白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子-α（TNF-α）促炎细胞因子以及抗炎细胞因子血红素加氧酶-1（HO-1）的表达水平。双荧光素酶报告基因实验评估 GAS5、miR-222-3p 和 TIMP3 之间的关联。结果显示，在 MPP 中 GAS5 和 TIMP3 的表达下调，miR-222-3p 的表达上调。GAS5 过表达可增加 LAMP 诱导的 THP-1 细胞活力。GAS5 过表达可降低 LAMP 诱导的 THP-1 细胞中 IL-1β、IL-6、TNF-α和 HO-1 的水平。GAS5 可与 miR-222-3p 直接相互作用。TIMP3 是 miR-222-3p 的靶基因。miR-222-3p 上调或 TIMP3 敲低可逆转 GAS5 过表达对 LAMP 诱导的 THP-1 细胞活力的促进作用以及对炎症的抑制作用。GAS5 过表达通过调节 miR-222-3p/TIMP3 轴增加 LAMP 诱导的 THP-1 细胞活力并降低其炎症。这些结果为 MPP 的治疗提供了潜在的治疗靶点。
Zotero 插件