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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse
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HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse

机译：HB-EGF促进气道平滑肌细胞及其祖细胞迁移有助于哮喘小鼠气道平滑肌重塑

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摘要

The airway smooth muscle (ASM) cells' proliferation, migration, and their progenitor's migration are currently regarded as causative factors for ASM remodeling in asthma. Heparin-binding epidermal growth factor (HB-EGF), a potent mitogen and chemotactic factor, could promote ASM cell proliferation through MAPK pathways. In this study, we obtained primary ASM cells and their progenitors from C57BL/6 mice and went on to explore the role of HB-EGF in these cells migration and the underlying mechanisms. We found that recombinant HB-EGF (rHB-EGF) intratracheal instillation accelerated ASM layer thickening in an OVA-induced asthmatic mouse. Modified Boyden chamber assay revealed that rHB-EGF facilitate ASM cell migration in a dose-dependent manner and ASM cells from asthmatic mice had a greater migration ability than that from normal counterparts. rHB-EGF could stimulate the phosphorylation of ERK1/2 and p38 in ASM cells but further migration assay showed that only epidermal growth factor receptor inhibitor (AG1478) or p38 inhibitor (SB203580), but not ERK1/2 inhibitor (PD98059), could inhibit rHB-EGF-mediated ASM cells migration. Actin cytoskeleton experiments exhibited that rHB-EGF could cause actin stress fibers disassembly and focal adhesions formation of ASM cells through the activation of p38. Finally, airway instillation of rHB-EGF promoted the recruitment of bone marrow-derived smooth muscle progenitor cells, which were transferred via caudal vein, migrating into the airway from the circulation. These observations demonstrated that ASM remodeling in asthma might have resulted from HB-EGF-mediated ASM cells and their progenitor cells migration, via p38 MAPK-dependent actin cytoskeleton remodeling.
机译：气道平滑肌（ASM）细胞的增殖，迁移及其祖细胞迁移目前被认为是哮喘ASM重塑的病因。肝素结合表皮生长因子（HB-EGF）是有效的促分裂原和趋化因子，可通过MAPK途径促进ASM细胞增殖。在这项研究中，我们从C57BL / 6小鼠获得了原代ASM细胞及其祖细胞，并继续探索HB-EGF在这些细胞迁移中的作用及其潜在机制。我们发现在OVA诱发的哮喘小鼠中，重组HB-EGF（rHB-EGF）气管内滴注可加速ASM层增厚。改良的Boyden室测定法显示，rHB-EGF以剂量依赖性方式促进ASM细胞迁移，哮喘小鼠的ASM细胞具有比正常小鼠更高的迁移能力。 rHB-EGF可以刺激ASM细胞中ERK1 / 2和p38的磷酸化，但进一步的迁移分析表明，只有表皮生长因子受体抑制剂（AG1478）或p38抑制剂（SB203580），而ERK1 / 2抑制剂（PD98059）不能抑制rHB-EGF介导的ASM细胞迁移。肌动蛋白细胞骨架实验显示，rHB-EGF可能通过激活p38引起肌动蛋白应激纤维分解和ASM细胞粘着斑形成。最后，rHB-EGF的气道滴注促进了骨髓来源的平滑肌祖细胞的募集，这些细胞通过尾静脉转移，并从循环系统迁移到气道中。这些观察结果表明，哮喘中的ASM重塑可能是由HB-EGF介导的ASM细胞及其祖细胞通过p38 MAPK依赖性肌动蛋白细胞骨架重塑而引起的。

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