Home General Physiology and Biophysics 2024 General Physiology and Biophysics Vol.43, No.1, p 37–48, 2024

Journal info


Quarterly, 80 pp. per issue
Founded: 1982
ISSN  1338-4325 (online)

Published in English

Aims and Scope
Editorial Info
Abstracting and Indexing
Submission Guidelines

Select Journal







Webshop Cart

Your Cart is currently empty.
Info: Your browser does not accept cookies. To put products into your cart and purchase them you need to enable cookies.

General Physiology and Biophysics Vol.43, No.1, p 37–48, 2024

Title: Inactivation of the TGF-β1/ALK5 axis enhances club cell function and alleviates lung tissue damage to ameliorate COPD progression through the MEK/ERK signaling pathway
Author: Jing Tian, Hui Ouyang, Jie Wu, Lu Wen, Xiaoping Li, Fangying Yang, Hao Yuan
Abstract: Chronic obstructive pulmonary disease (COPD) is a highly prevalent and fatal disease worldwide. The function of club cells, which are considered progenitor/stem cells of the bronchial epithelium, and their secreted protein CC16, have been proposed as potential targets for COPD treatment. This study aimed to investigate the role of the TGF-β1/ALK5 signaling pathway in club cell function and COPD progression. C57BL/6J mice were divided into Normal group (exposed to fresh air) and COPD group (exposed to incremental cigarette smoke extract for 12 weeks). The COPD mice were further divided into COPD group, DMSO group, and LY2109761 group (injected with 150 mg/kg LY2109761, a TGF-β1 inhibitor). Tissue staining was used to assess lung damage, and the expression of CC16 was measured. The levels of inflammatory factors and DNA damage-related indicators were also measured. The involvement of the MEK/ERK signaling pathway was determined. COPD mice exhibited severe lung damage and impaired club cell function. Activation of the TGF-β1/ALK5 and MEK/ERK pathways were observed in COPD mice. However, administration of LY2109761 in COPD mice inactivated the TGF-β1/ALK5 and MEK/ERK pathways. Administration of LY2109761 also alleviated pulmonary fibrosis, downregulated the levels cleaved caspase-3, IL-4, IL-5, IL-13, IL-12, and IFN-γ, and limited the phosphorylation of Chk1. Moreover, LY2109761 enhanced CC16 expression and decreased lung cell apoptosis. Inactivation of the TGF-β1/ALK5 axis inhibits the MEK/ERK signaling pathway, enhances club cell function, and alleviates lung tissue damage. These findings suggest that TGF-β1 is a potential therapeutic target for COPD.
Keywords: TGF-β1/ALK5 — MEK/ERK — Club cell — COPD
Published online: 17-Jan-2024
Year: 2024, Volume: 43, Issue: 1 Page From: 37, Page To: 48
doi:10.4149/gpb_2023034


download file


© AEPress s.r.o
Copyright notice: For any permission to reproduce, archive or otherwise use the documents in the ELiS, please contact AEP.