Ito Yuho, Iwashita Jun, Murata Jun
Environmental Protection Division, Research Center for Public Health and Environment, Akita, Japan.
Faculty of Bioresource Sciences, Akita Prefectural University, 241-438 Kaidobata-Nishi, Shimoshino-Nakano, Akita, Akita, 010-0195, Japan.
Biochem Biophys Rep. 2019 Nov 8;20:100707. doi: 10.1016/j.bbrep.2019.100707. eCollection 2019 Dec.
Mucin 5AC (MUC5AC) hypersecretion induces airway narrowing in patients with asthma, which leads to breathing problems. We investigated the regulation of MUC5AC secretion by extracellular matrix (ECM) proteins in human primary airway epithelial cells from patients with asthma. The addition of type IV collagen to three-dimensional cultured human primary airway epithelial cells, which mimics the airway surface, reduced MUC5AC secretion in the medium, while the addition of laminin increased MUC5AC secretion. Furthermore, the addition of fibronectin did not affect MUC5AC secretion. In particular, the repeated addition of a low concentration of type IV collagen demonstrated a cumulative effect on the reduction in MUC5AC secretion. Human primary cells incubated with type IV collagen showed downregulated extracellular signal-regulated kinase (ERK) activity, which induced MUC5AC hypersecretion but did not affect Akt activity. These results suggest that the addition of type IV collagen to the apical surface of primary cells downregulates MUC5AC secretion and has a cumulative effect on MUC5AC secretion which might be effected via the ERK signaling pathway.
粘蛋白5AC（MUC5AC）分泌过多会导致哮喘患者气道狭窄，进而引发呼吸问题。我们研究了细胞外基质（ECM）蛋白对哮喘患者人原代气道上皮细胞中MUC5AC分泌的调节作用。将IV型胶原添加到模拟气道表面的三维培养人原代气道上皮细胞中，可减少培养基中MUC5AC的分泌，而添加层粘连蛋白则会增加MUC5AC的分泌。此外，添加纤连蛋白对MUC5AC的分泌没有影响。特别是，重复添加低浓度的IV型胶原对MUC5AC分泌的减少具有累积效应。用IV型胶原孵育的人原代细胞显示细胞外信号调节激酶（ERK）活性下调，ERK活性可诱导MUC5AC分泌过多，但不影响Akt活性。这些结果表明，将IV型胶原添加到原代细胞的顶端表面可下调MUC5AC的分泌，并对MUC5AC的分泌产生累积效应，这可能是通过ERK信号通路实现的。
