Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma

Haiying Peng; Fei Sun; Yunxiu Jiang; Zihan Guo; Xinyi Liu; Anli Zuo; Degan Lu

doi:10.3389/fimmu.2023.1167605

Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma

Front Immunol. 2023 Nov 1:14:1167605. doi: 10.3389/fimmu.2023.1167605. eCollection 2023.

Authors

Haiying Peng¹, Fei Sun¹, Yunxiu Jiang¹, Zihan Guo¹, Xinyi Liu¹, Anli Zuo¹, Degan Lu¹

Affiliation

¹ Department of Respiratory, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan, China.

Abstract

Background: TGF-β1 can induce epithelial-mesenchymal transition (EMT) in primary airway epithelial cells (AECs). Semaphorin7A (Sema7a) plays a crucial role in regulating immune responses and initiating and maintaining transforming growth factor β1 TGF-β1-induced fibrosis.

Objective: To determine the expression of Sema7a, in serum isolated from asthmatics and non-asthmatics, the role of Sema7a in TGF-β1 induced proliferation, migration and airway EMT in human bronchial epithelial cells (HBECs) in vitro.

Methods: The concentrations of Sema7a in serum of asthmatic patients was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Sema7a and integrin-β1 were examined using conventional western blotting and real-time quantitative PCR (RT-PCR). Interaction between the Sema7a and Integrin-β1 was detected using the Integrin-β1 blocking antibody (GLPG0187). The changes in EMT indicators were performed by western blotting and immunofluorescence, as well as the expression levels of phosphorylated Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) were analyzed by western blot and their mRNA expression was determined by RT-PCR.

Results: We described the first differentially expressed protein of sema7a, in patients with diagnosed bronchial asthma were significantly higher than those of healthy persons (P<0.05). Western blotting and RT-PCR showed that Sema7a and Integrin-β1 expression were significantly increased in lung tissue from the ovalbumin (OVA)-induced asthma model. GLPG0187 inhibited TGF-β1-mediated HBECs EMT, proliferation and migration, which was associated with Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) phosphorylation.

Conclusion: Sema7a may play an important role in asthma airway remodeling by inducing EMT. Therefore, new therapeutic approaches for the treatment of chronic asthma, could be aided by the development of agents that target the Sema7a.

Keywords: TGF-β1; airway remodeling; asthma; epithelial-mesenchymal transition; semaphorin 7A.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asthma* / metabolism
Epithelial-Mesenchymal Transition
Humans
Integrins / metabolism
MAP Kinase Signaling System
Semaphorins* / genetics
Semaphorins* / metabolism
Signal Transduction
Transforming Growth Factor beta1 / metabolism

Substances

GLPG0187
Integrins
Semaphorins
Transforming Growth Factor beta1
SEMA7A protein, human

Grants and funding

This work was supported by the Collaborative Innovation Center for Intelligent Molecules with Multi effects and Nanomedicine (No. 2019-01), Shandong Province, China; Shandong Provincial Natural Science Foundation (ZR2021LSW015) and Jinan Clinical Medicine Research Program for Respiratory disease (No. 202132002). The funders did not play a role in the design of the study, the collection and analysis of the data, or the decision to prepare and publish this manuscript.