Iwashita Jun, Maeda Hikari, Ishimura Momo, Murata Jun
Faculty of Bioresource Sciences, Akita Prefectural University, Akita, Japan.
Front Pharmacol. 2022 Sep 16;13:851374. doi: 10.3389/fphar.2022.851374. eCollection 2022.
Mucin 5AC (MUC5AC) is excessively secreted in the respiratory tract of patients with asthma. Suppressing this secretion is important for improving the air passages, which facilitates easy breathing. We have previously reported that the addition of type IV collagen, a typical extracellular matrix (ECM) protein, to the culture medium for human cell lines and primary cells reduced MUC5AC secretion. In this report, we further investigated the effect of type IV collagen on MUC5AC secretion . We employed ovalbumin (OVA)-sensitized mice to model of asthma and exposed them to type IV collagen to verify the reducing effect of MUC5AC . The amount of MUC5AC in bronchoalveolar lavage fluid was examined after nebulization of type IV collagen. Hypersecretion of MUC5AC of the OVA-sensitized mice was suppressed by type IV collagen exposure in a time- and dose-dependent manner. Furthermore, type IV collagen exposure to OVA-sensitized mice decreased integrin α2 and β1 expression in the lungs and increased the levels of Akt and extracellular signal-regulated kinase (ERK) phosphorylation in the trachea. These results suggest that type IV collagen suppresses MUC5AC hypersecretion modulating integrin expression and Akt/ERK phosphorylation in the respiratory tract of the OVA-sensitized mice.
黏蛋白5AC(MUC5AC)在哮喘患者的呼吸道中过度分泌。抑制这种分泌对于改善气道很重要,有助于轻松呼吸。我们之前报道过,向人细胞系和原代细胞的培养基中添加典型的细胞外基质(ECM)蛋白IV型胶原可减少MUC5AC的分泌。在本报告中,我们进一步研究了IV型胶原对MUC5AC分泌的影响。我们使用卵清蛋白(OVA)致敏的小鼠作为哮喘模型,并让它们接触IV型胶原以验证其对MUC5AC的减少作用。在雾化IV型胶原后,检测支气管肺泡灌洗液中MUC5AC的含量。OVA致敏小鼠的MUC5AC过度分泌通过接触IV型胶原以时间和剂量依赖性方式受到抑制。此外,让OVA致敏小鼠接触IV型胶原会降低肺中整合素α2和β1的表达,并增加气管中Akt和细胞外信号调节激酶(ERK)磷酸化水平。这些结果表明,IV型胶原通过调节OVA致敏小鼠呼吸道中的整合素表达和Akt/ERK磷酸化来抑制MUC5AC的过度分泌。