Duvelisib attenuates bleomycin-induced pulmonary fibrosis via inhibiting the PI3K/Akt/mTOR signalling pathway

Area of Science:

• Pulmonary Medicine
• Pharmacology
• Cell Biology

Background:

• Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear pathogenesis and limited treatments.
• Myofibroblasts drive IPF by excessive extracellular matrix deposition, making their activation and autophagy a therapeutic target.
• The PI3K/Akt/mTOR pathway is crucial in fibroblast activation and autophagy inhibition during lung fibrosis.

Purpose of the Study:

• To investigate the therapeutic potential of Duvelisib, a PI3K inhibitor, in treating pulmonary fibrosis.
• To evaluate Duvelisib's effects on lung fibroblast activation and autophagy in vitro and in vivo.
• To elucidate the underlying pharmacological mechanisms of Duvelisib in pulmonary fibrosis.

Main Methods:

• A mouse model of bleomycin-induced pulmonary fibrosis was utilized for in vivo studies.
• In vitro experiments were conducted on lung fibroblasts to explore cellular mechanisms.
• Duvelisib's effects on collagen deposition, pulmonary function, fibroblast activation, and PI3K/Akt/mTOR pathway phosphorylation were assessed.

Main Results:

• Duvelisib significantly reduced collagen deposition and improved lung function in the bleomycin-induced pulmonary fibrosis model.
• In vitro and in vivo studies demonstrated Duvelisib's dose-dependent suppression of lung fibroblast activation.
• Duvelisib treatment improved autophagy inhibition by downregulating PI3K, Akt, and mTOR phosphorylation.

Conclusions:

• Duvelisib effectively alleviates the severity of pulmonary fibrosis.
• Duvelisib demonstrates potential as a therapeutic agent for pulmonary fibrosis by targeting fibroblast activation and autophagy.
• Inhibition of the PI3K/Akt/mTOR pathway is a key mechanism for Duvelisib's antifibrotic effects.