A74-01 Gp130 Promotes Airway Remodeling After Injury by Activating Pgk1

Abstract Rationale Tracheal fibrosis, which leads to airway stenosis, is characterized by fibroblast activation and extracellular matrix (ECM) deposition. Glycolytic reprogramming has been linked to this activation; however, its regulatory mechanisms in the context of fibrosis remain unclear. This study investigates the role of GP130. Methods Utilizing both in vitro and in vivo models, we evaluated proliferation, activation (α-SMA), ECM components (Collagen I), and glycolysis using CCK-8 assays, flow cytometry, and Western blotting techniques. A rat model of tracheal injury was employed to assess the effects of GP130 intervention on stenosis, ECM composition, and PGK1 levels. The interaction between GP130 and PGK1 was examined via co-immunoprecipitation (Co-IP). Results We found that GP130 expression was significantly upregulated in fibrotic tissues as well as in activated fibroblasts. Overexpression of GP130 enhanced fibroblast activation, proliferation, ECM synthesis, and glycolytic activity. Notably, GP130 was shown to interact with PGK1; inhibition of PGK1 effectively reversed these observed effects. Furthermore, suppression of GP130 in vivo mitigated fibrosis-related changes by improving stenosis and reducing ECM accumulation. Conclusion Our findings indicate that GP130 plays a pivotal role in promoting tracheal fibrosis by driving glycolysis through PGK1 modulation. Targeting the GP130/PGK1 axis presents a promising therapeutic strategy for addressing tracheal fibrosis. This abstract is funded by: none