Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, which was caused by a complex interplay of inflammatory responses and chronic damage. miR-21 is increased in patients with IPF, but its function in the embryonic lung-derived diploid fibroblasts cells subjected to LPS is elusive. miRNA expression profile was obtained from GEO database and target genes of miRNAs were forecasted by TargetScan. To mimic the LPS-induced injury, different concentrations of LPS were applied to treat WI-38 cells. Functional in vitro experiments were conducted to examine the role of miR-21 and TIMP3. Luciferase report assay was performed to verify the relationship between miR-21 and TIMP3. qRT-PCR, western blotting, and ELISA were conducted to detect the levels of the related miRNAs, proteins, and inflammatory factors. miR-21 presented higher levels in interstitial pneumonia patients and LPS-induced WI-38 cells. Overexpression of miR-21 was negatively correlated with the proliferative capability of LPS-treated WI-38 cells. miR-21 directly targets TIMP3. TIMP3 restored the suppressive impact of miR-21 mimic on the proliferation, while TIMP3 alleviated the promoting impact of miR-21 mimic on the apoptosis of WI-38 cells treated by LPS. miR-21 inhibited Bcl-2 but increased Bax, cleaved caspase-3, and cleaved caspase-9. Besides, miR-21 elevated the levels of IL-6 and IL-β but reduced the IL-10, which were weakened by TIMP3. Totally, miR-21 aggravated the LPS-induced lung injury and modulated inflammatory responses by targeting TIMP3.

特发性肺纤维化（IPF）是一种进行性肺部疾病，由炎症反应和慢性损伤的复杂相互作用引起。 miR-21 在 IPF 患者中增加，但其在接受 LPS 的胚胎肺源性二倍体成纤维细胞中的功能尚不清楚。从GEO数据库中获取miRNA表达谱，并通过TargetScan预测miRNA的靶基因。为了模拟 LPS 诱导的损伤，使用不同浓度的 LPS 处理 WI-38 细胞。进行功能性体外实验来检查 miR-21 和 TIMP3 的作用。进行荧光素酶报告分析以验证 miR-21 和 TIMP3 之间的关系。采用qRT-PCR、western blotting和ELISA检测相关miRNA、蛋白和炎症因子的水平。 miR-21 在间质性肺炎患者和 LPS 诱导的 WI-38 细胞中呈现较高水平。 miR-21 的过表达与 LPS 处理的 WI-38 细胞的增殖能力呈负相关。 miR-21 直接靶向 TIMP3。 TIMP3恢复了miR-21模拟物对LPS处理的WI-38细胞增殖的抑制作用，而TIMP3减轻了miR-21模拟物对细胞凋亡的促进作用。 miR-21 抑制 Bcl-2，但增加 Bax、裂解的 caspase-3 和裂解的 caspase-9。此外，miR-21 升高了 IL-6 和 IL-β 的水平，但降低了 IL-10 的水平，而 TIMP3 则减弱了 IL-10 的水平。总体而言，miR-21 通过靶向 TIMP3 加重了 LPS 诱导的肺损伤并调节炎症反应。