PTPRH Alleviates Airway Obstruction and Th2 Inflammation in Asthma as a Protective Factor.
PTPRH Alleviates Airway Obstruction and Th2 Inflammation in Asthma as a Protective Factor.
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DOI：
10.2147/jaa.s340059
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发表时间：
2022
影响因子：
3.2
通讯作者：
Guo YB
中科院分区：
文献类型：
--
作者：
Chen FJ;Du LJ;Zeng Z;Huang XY;Xu CY;Tan WP;Xie CM;Liang YX;Guo YB
PTPRH在癌症患者中直接抑制EGFR活性，并且活化的EGFR在哮喘中诱导杯状细胞增生和粘液高分泌。然而，PTPRH在哮喘中的功能仍不清楚。本研究旨在探讨PTPRH与哮喘的关系及其可能机制。我们检测了哮喘患者（n = 108）和健康对照（n = 35）的PTPRH水平，并分析了PTPRH与哮喘相关指标之间的相关性。建立PTPRH转染人支气管上皮细胞（HBECs）和哮喘小鼠模型，研究PTPRH的功能。PTPRH的表达显著增加，并与肺功能参数相关，包括气道阻塞，和T辅助细胞2（Th 2）相关的标志物在哮喘患者。PTPRH在屋尘螨（HDM）诱导的哮喘小鼠中增加，而用PTPRH治疗时，Th 2气道炎症和Muc 5ac被抑制。因此，PTPRH表达在IL-13刺激的HBEC中显著增加，但PTPRH过表达抑制MUC 5AC。转染PTPRH的HBECs对EGFR、ERK 1/2和AKT的磷酸化有抑制作用，而对EGFR、ERK 1/2和AKT去磷酸化的HBECs有诱导作用。PTPRH可能通过磷酸化EGFR/ERK 1/2/AKT信号通路，减少MUC 5AC分泌，从而减轻哮喘气道阻塞。
PTPRH inhibits EGFR activity directly in cancer patients and activated EGFR induces goblet cell hyperplasia and mucus hypersecretion in asthma. However, the function of PTPRH in asthma remains unknown. The purpose of this study was to access the association of PTPRH with asthma and its underlying mechanism. We examined the PTPRH level in asthma patients (n = 108) and healthy controls (n = 35), and analyzed the correlations between PTPRH and asthma-related indicators. Human bronchial epithelial cell (HBECs) transfected with PTPRH and asthma mouse model were set up to investigate the function of PTPRH. The expression of PTPRH was significantly increased and correlated with pulmonary function parameters, including airway obstruction, and T-helper2 (Th2) associated markers in asthma patients. PTPRH increased in the house dust mite (HDM)-induced asthmatic mice, while Th2 airway inflammation and Muc5ac suppressed when treated with PTPRH. Accordingly, PTPRH expression was markedly increased in IL-13-stimulated HBECs but PTPRH over-expression suppressed MUC5AC. Moreover, HBECs transfected with over-expressed PTPRH inhibited the phosphorylation of EGFR, ERK1/2 and AKT, while induced against PTPRH in HBECs dephosphorylated of EGFR, ERK1/2 and AKT. PTPRH reduces MUC5AC secretion to alleviate airway obstruction in asthma via potential phosphorylating of EGFR/ERK1/2/AKT signaling pathway, which may provide possible therapeutic implications for asthma.