Department of Pediatrics, Maternal and Child Health Hospital of Shandong Province, Jinan, Shandong 250014, China.
Department of Common Pediatric, Shandong Cao County People's Hospital, Heze, Shandong 250014, China.
J Healthc Eng. 2022 Mar 24;2022:7099097. doi: 10.1155/2022/7099097. eCollection 2022.
Osthole, a coumarin compound derived from Fructus Cnidii, exerts anti-inflammatory effects in an asthma model. But the effect of osthole on epithelial injury and epithelial-mesenchymal transition (EMT) in asthma remains unclear. 16HBE cells were incubated with TGF-1 with or without osthole in vitro. Ovalbumin (OVA)-induced asthmatic mouse model was established in vivo. Cell counting kit-8 was carried out to evaluate the viability of 16HBE cells. The impact of osthole on TGF-1-evoked cell apoptosis and EMT process was measured by flow cytometry based on Annexin V-FITC/PI staining, transwell assay, immunofluorescence, and Western blot. The regulatory role of osthole in TGF-1/Smad and p38, ERK1/2, and JNK MAPK signaling was detected via Western blot. Osthole treatment significantly suppressed TGF-1-induced 16HBE cell apoptosis, verified by a reduced percentage of apoptotic cells, decreased expression of proapoptotic proteins (cleaved-caspase3 and Bax), and enhanced antiapoptotic factor (Bcl-2) expression. In addition, the promotive impact of TGF-1 on the migration of 16HBE cells was reversed by osthole, accompanied by elevated E-cadherin expression and reduced Snail and N-cadherin expression. The activation of the Smad2/3 and MAPKs pathway evoked by TGF-1 was inhibited by osthole in 16HBE cells. We also found that osthole mitigated airway epithelium injury and subepithelial fibrosis in OVA-challenged asthmatic mice in vivo. Osthole could mitigate TGF-1-induced epithelial cell injury and EMT process by suppressing the activation of MAPK and Smad2/3 pathways separately. Our present study showed a new insight into understanding the underlying mechanism of osthole injury on epithelium injury and subepithelial fibrosis in airway remodeling. Asthma, epithelial injury, epithelial-mesenchymal transition, and airway remodeling are the effects of osthole on airway remodeling.
蛇床子素是一种源自蛇床子的香豆素化合物，在哮喘模型中具有抗炎作用。但蛇床子素对哮喘中上皮损伤和上皮-间充质转化（EMT）的影响尚不清楚。体外将 TGF-β1 与蛇床子素孵育于 16HBE 细胞。在体内建立卵清蛋白（OVA）诱导的哮喘小鼠模型。通过细胞计数试剂盒-8 评估 16HBE 细胞的活力。通过 Annexin V-FITC/PI 染色、transwell 测定、免疫荧光和 Western blot 测定，研究蛇床子素对 TGF-β1 诱导的细胞凋亡和 EMT 过程的影响。通过 Western blot 检测蛇床子素对 TGF-β1/Smad 和 p38、ERK1/2 和 JNK MAPK 信号通路的调节作用。蛇床子素处理显著抑制 TGF-β1 诱导的 16HBE 细胞凋亡，表现为凋亡细胞比例降低，促凋亡蛋白（cleaved-caspase3 和 Bax）表达降低，抗凋亡因子（Bcl-2）表达增强。此外，蛇床子素逆转了 TGF-β1 对 16HBE 细胞迁移的促进作用，同时伴随着 E-钙黏蛋白表达升高和 Snail 和 N-钙黏蛋白表达降低。蛇床子素抑制了 TGF-β1 激活的 16HBE 细胞中 Smad2/3 和 MAPKs 通路的激活。我们还发现，蛇床子素减轻了 OVA 激发的哮喘小鼠气道上皮损伤和亚上皮纤维化。蛇床子素通过抑制 MAPK 和 Smad2/3 通路的激活来减轻 TGF-β1 诱导的上皮细胞损伤和 EMT 过程。本研究为理解蛇床子素对气道重塑中上皮损伤和亚上皮纤维化的作用机制提供了新的认识。哮喘、上皮损伤、上皮-间充质转化和气道重塑是蛇床子素对气道重塑的影响。
