PTPRH Alleviates Airway Obstruction and Th2 Inflammation in Asthma as a Protective Factor

Feng-Jia Chen; Li-Juan Du; Zhimin Zeng; Xin-Yan Huang; Chang-Yi Xu; Wei-Ping Tan; Can-Mao Xie; Yu-Xia Liang; Yu-Biao Guo

doi:10.2147/JAA.S340059

PTPRH Alleviates Airway Obstruction and Th2 Inflammation in Asthma as a Protective Factor

J Asthma Allergy. 2022 Feb 2:15:133-144. doi: 10.2147/JAA.S340059. eCollection 2022.

Authors

Feng-Jia Chen^#^{1

2}, Li-Juan Du^#^{1

2}, Zhimin Zeng^#^{1

2}, Xin-Yan Huang^{1

2}, Chang-Yi Xu^{1

2}, Wei-Ping Tan^{1

2}, Can-Mao Xie^{1

2}, Yu-Xia Liang^{1

2}, Yu-Biao Guo^{1

2}

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
² Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: EGFR/ERK1/2/AKT; MUC5AC; PTPRH; asthma; human bronchial epithelial cells.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81770024); Natural Science Foundation of Guangdong Province (2021A1515012027); China Postdoctoral Science Foundation (2020M683124); Guangdong Finance Foundation for Industrial Technology Research and Development(20160907).