Airway remodeling is a primary pathological feature of
asthma. The current
therapy for
asthma mainly targets reducing
inflammation but not particularly
airway remodeling. Therefore, it is worthwhile to develop alternative and more effective
therapies to attenuate remodeling.
Gu-Ben-Fang-Xiao Decoction (GBFXD) has been used to effectively and safely treat
asthma for decades. In this study, GBFXD regulated airway
inflammation,
collagen deposition, and the molecules relevant to
airway remodeling such as
Vimentin, α-SMA,
hydroxyproline, and
E-cadherin in chronic remission
asthma (CRA) murine model. Proteomic analysis indicated that the overlapping differentially expressed
proteins (DEPs) (Model/Control and GBFXD/Model) were mainly
collagens and laminins, which were extracellular matrix (ECM)
proteins. In addition, the KEGG analysis showed that GBFXD could regulate pathways related to
airway remodeling including ECM-receptor interactions, focal adhesion, and the PI3K/AKT signaling pathway, which were the top three significantly enriched pathways containing the most DEPs for both Model/Control and GBFXD/Model. Further validation research showed that GBFXD regulated reticulon-4 (RTN4) and suppressed the activation of the PI3K/AKT pathway to alleviate ECM
proteins deposition. In conclusion, our findings indicate that GBFXD possibly regulate the PI3K/AKT pathway via RTN4 to improve
airway remodeling, which provides a new insight into the molecular mechanism of GBFXD for the treatment of CRA.