Objective: This study evaluates the role of macrophage intracellular tyrosine phosphatase PTP1B in slowing the progression of Chronic Obstructive Pulmonary Disease (COPD) through the inhibition of the SHP-2/Src/ERK1/2/NLRP3 signaling pathway.
Methods: We administered PTP1B non-targeting control (NC) and PTP1B overexpression (OE) lentiviruses to mice. Post-infection, lung tissues underwent Hematoxylin and Eosin (HE) staining and immunofluorescence analysis to detect PTP1B, SHP2, Src, and FAK protein levels. We also examined CD68+ expression in RAW264.7 macrophages infected with either PTP1B NC or OE lentiviruses, or stimulated with Cigarette Smoke Extract (CSE), categorizing them into four groups for further analysis. Western blotting identified changes in protein expression of ERK1/2, NOX2, NOX3, NFΚB, NLRP3, IL-1β, and TNFα. Additionally, immunofluorescence staining assessed the expression of CD68, SHP2, and Src.
Results: Overexpression of PTP1B notably diminished lung tissue damage in COPD mice compared to the NC group, demonstrating a significant reduction in PTP1B, SHP2, Src, and FAK protein levels, alongside decreased CD68+ fluorescence. Western blot results revealed a marked decrease in the expression levels of ERK1/2, NOX2, NOX3, NFΚB, NLRP3, IL-1β, and TNFα proteins. Immunofluorescence further highlighted a substantial reduction in SHP2 and Src expressions in the PTP1B OE+CSE group versus the PTP1B NC+CSE group.
Conclusion: Our findings suggest that macrophage intracellular tyrosine phosphatase PTP1B plays a critical role in delaying COPD progression by targeting the SHP-2/Src/ERK1/2/NLRP3 signaling pathway, underscoring its potential as a therapeutic target in COPD management.