LXA4 inhibits TGF-β1-induced airway smooth muscle cells proliferation and migration by suppressing the Smad/YAP pathway
LXA4 inhibits TGF-β1-induced airway smooth muscle cells proliferation and migration by suppressing the Smad/YAP pathway
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DOI：
10.1016/j.intimp.2023.110144
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发表时间：
2023-04-07
影响因子：
5.6
通讯作者：
Liu，Lu
中科院分区：
文献类型：
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作者：
Zhao，Yali;Zhang，Xiangli;Liu，Lu
本研究旨在探讨转化生长因子-β1（transforminggrowthfactor-β1，TGF-β1）诱导大鼠气道平滑肌细胞（airwaysmoothmuscle cells，ASMCs）增殖和迁移的信号转导机制，并探讨脂氧素A4（lipoxinA 4，LXA 4）对TGF-β1诱导的大鼠气道平滑肌细胞增殖和迁移的影响及其机制。TGF-β1通过激活Smad 2/3上调转录辅激活因子Yes相关蛋白（雅普）的表达，进而上调cyclin D1的表达，导致大鼠ASMCs增殖和迁移。TGF-β1受体抑制剂SB 431542可逆转上述效应。雅普是TGF-β1诱导ASMCs增殖和迁移的重要介质。敲低雅普可破坏TGF-β1的气道重塑功能。LXA 4预孵育大鼠ASMCs可阻断TGF-β1诱导的Smad 2/3活化，改变其下游靶点雅普和cyclin D1，从而抑制大鼠ASMCs的增殖和迁移。本研究提示LXA 4通过抑制Smad/雅普信号通路抑制大鼠ASMCs增殖和迁移，可能通过负性调节气道重塑来防治哮喘。
The aims of the present study were to examine the signaling mechanisms for transforming growth factor-β1 (TGF-β1)-induced rat airway smooth muscle cells (ASMCs) proliferation and migration and to determine the effect of lipoxin A4 (LXA4) on TGF-β1-induced rat ASMCs proliferation and migration and its underlying mechanisms. TGF-β1 upregulated transcriptional coactivator Yes-associated protein (YAP) expression by activating Smad2/3 and then upregulated cyclin D1, leading to rat ASMCs proliferation and migration. This effect was reversed after treatment with the TGF-β1 receptor inhibitor SB431542. YAP is a critical mediator of TGF-β1-induced ASMCs proliferation and migration. Knockdown of YAP disrupted the pro-airway remodeling function of TGF-β1. Preincubation of rat ASMCs with LXA4 blocked TGF-β1-induced activation of Smad2/3 and changed its downstream targets, YAP and cyclin D1, resulting in the inhibition of rat ASMCs proliferation and migration. Our study suggests that LXA4 suppresses Smad/YAP signaling to inhibit rat ASMCs proliferation and migration and therefore has potential value in the prevention and treatment of asthma by negatively modulating airway remodeling.