Childhood asthma is a common respiratory disease characterized by airway inflammation. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) has been found to be involved in the progression of asthma. This study aimed to explore the role of TIPE2 in the regulation of airway smooth muscle cells (ASMCs), which are one of the main effector cells in the development of asthma. ASMCs were transfected with pcDNA3.0-TIPE2 or si-TIPE2 for 48 h and then treated with platelet-derived growth factor (PDGF)-BB. Cell proliferation of ASMCs was measured using the MTT assay. Cell migration of ASMCs was determined by a transwell assay. The mRNA expression levels of calponin and smooth muscle protein 22α (SM22α) were measured using qRT-PCR. The levels of TIPE2, calponin, SM22α, PI3K, p-PI3K, Akt, and p-Akt were detected by Western blotting. Our results showed that PDGF-BB treatment significantly reduced TIPE2 expression at both the mRNA and protein levels in ASMCs. Overexpression of TIPE2 inhibited PDGF-BB-induced ASMC proliferation and migration. In addition, overexpression of TIPE2 increased the expression of calponin and SM22α in PDGF-BB-stimulated ASMCs. However, an opposite effect was observed with TIPE2 knockdown. Furthermore, TIPE2 overexpression blocked PDGF-BB-induced phosphorylation of PI3K and Akt, whereas the expression of p-PI3K and p-Akt were aggravated by TIPE2 knockdown. Additionally, the effects of TIPE2 overexpression and TIPE2 knockdown were altered by IGF-1 and LY294002 treatments, respectively. Our findings demonstrate that TIPE2 inhibits PDGF-BB-induced ASMC proliferation, migration, and phenotype switching via the PI3K/Akt signaling pathway. Thus, TIPE2 may be a potential therapeutic target for the treatment of asthma.

中文翻译：

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TIPE2 通过 PI3K/Akt 信号通路抑制 PDGF-BB 诱导的气道平滑肌细胞表型转换

儿童哮喘是一种以气道炎症为特征的常见呼吸道疾病。已发现肿瘤坏死因子-α 诱导的蛋白 8 样 2 (TIPE2) 与哮喘的进展有关。本研究旨在探讨 TIPE2 在调节气道平滑肌细胞 (ASMCs) 中的作用，ASMCs 是哮喘发展过程中的主要效应细胞之一。用 pcDNA3.0-TIPE2 或 si-TIPE2 转染 ASMC 48 小时，然后用血小板衍生生长因子 (PDGF)-BB 处理。使用 MTT 测定法测量 ASMC 的细胞增殖。ASMC 的细胞迁移由 transwell 测定法确定。使用 qRT-PCR 测量钙调蛋白和平滑肌蛋白 22α (SM22α) 的 mRNA 表达水平。Western blotting检测TIPE2、calponin、SM22α、PI3K、p-PI3K、Akt和p-Akt的水平。我们的结果表明，PDGF-BB 治疗显着降低了 ASMC 中 mRNA 和蛋白质水平的 TIPE2 表达。TIPE2 的过表达抑制 PDGF-BB 诱导的 ASMC 增殖和迁移。此外，TIPE2 的过表达增加了 PDGF-BB 刺激的 ASMC 中 calponin 和 SM22α 的表达。然而，使用 TIPE2 敲低观察到相反的效果。此外，TIPE2 过表达阻断了 PDGF-BB 诱导的 PI3K 和 Akt 磷酸化，而 TIPE2 敲低加剧了 p-PI3K 和 p-Akt 的表达。此外，IGF-1 和 LY294002 处理分别改变了 TIPE2 过表达和 TIPE2 敲低的影响。我们的研究结果表明，TIPE2 通过 PI3K/Akt 信号通路抑制 PDGF-BB 诱导的 ASMC 增殖、迁移和表型转换。因此，