Function of AMPK/mTOR Signaling in TGF-β1-Induced Pterygium Fibroblast Proliferation and Transdifferentiation

PURPOSE: This study aimed to investigate the regulatory role of the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling pathway in mediating transforming growth factor-beta 1 (TGF-β1)-induced cellular proliferation and transdifferentiation processes in human pterygium fibroblasts (HPFs). METHODS: qPCR and western blotting for PCNA, α-SMA, and pathway components. This comprehensive approach delineated the AMPK/mTOR axis as a critical regulator of TGF-β1-driven fibrotic phenotype acquisition in HPFs. RESULTS: Following TGF-β1 pretreatment-induced activation of human HPFs, both cell viability and migratory capacity were markedly enhanced, with concomitant upregulation of PCNA and α-SMA. Compound C-mediated AMPK inhibition potentiated the TGF-β1-induced enhancements in HPFs viability and migration rate, concomitant with reduced p-AMPK/AMPK ratio and elevated expression of PCNA, α-SMA, and p-mTOR/mTOR ratio. Conversely, AICAR-driven AMPK activation attenuated TGF-β1-stimulated effects, demonstrating diminished viability, suppressed migratory capacity, increased p-AMPK/AMPK ratio, and decreased expression of PCNA, α-SMA, and p-mTOR/mTOR ratio. CONCLUSIONS: This study demonstrates the critical regulatory role of the AMPK/mTOR signaling pathway in controlling TGF-β1-induced proliferation and transdifferentiation in HPFs, thereby providing a potential mechanistic framework for developing novel therapeutic interventions targeting fibrotic ocular surface disorders.