Work

LncRNA GAS5 attenuates COPD pathogenesis by stabilizing p120 catenin to suppress NF-κB-driven inflammation

Year: 2025

Type: article

Abstract: OBJECTIVE: To investigate the role of lncRNA GAS5 in COPD and its underlying mechanism. METHODS: COPD mouse model was conducted as an in vivo inflammatory response model. CSE was used to stimulate human airway epithelial cells (16HBE) and human normal lung epithelial cells (BEAS-2B) to establish an in vitro inflammatory response model. Recombinant adenoviruses containing GAS5 or GAS5 shRNA were used to overexpression or knockdown of GAS5. The expression of p120/NF-κB was detected by RT-PCR and Western Blot. The distribution of NF-κB p65 protein in cells was detected by western blot and immunofluorescence staining. The expression levels of IL-6, IL-8 and TNF-α in downstream NF-κB were detected by RT-PCR and ELISA. RESULT: The expression of lncRNA GAS5 was downregulated in COPD in vivo and in vitro. We showed that overexpression of GAS5 alleviates inflammation and NF-κB activation in COPD in vivo and in vitro. Moreover, we demonstrated that GAS5 regulate NF-κB activation by bind with p120. Knocking down of p120 inhibits the protective effect of GAS5 on inflammation. CONCLUSION: LncRNA GAS5 can bind with p120, enhance p120 stability and inhibit the NF-κB pathway and production of inflammatory factors downstream of NF-κB, thus playing a protective role in the airway.

Source: Respiratory Research

DOI: 10.1186/s12931-025-03445-w