Introduction: Our previous studies have shown that aberrant arterial remodelling occurs in IPF patients, and EndMT contributes to such remodelling changes. 

Aim: We aim to evaluate EndMT drivers in size-based pulmonary arteries from IPF patients compared to healthy controls (HC). 

Methods: Lung resections from IPF (n=13) and HC (n=11) were immunohistochemically stained for EndMT drivers: TGF-?1, pSmad-2/3, Smad-7, and ?-catenin, and analysed for their expression in intima, media, and adventitia of the pulmonary arteries. All analysis was done using microscope-assisted Image ProPlus7.0 software. 

Results: Compared to HC, increased expression of TGF-?1, pSmad-2/3, Smad-7, and ?-catenin were seen in all arterial sizes of IPF patients (p<0.05), particularly in the intimal layer (p<0.001). Intimal TGF-?1 and ?-catenin expression showed a significant association with the intimal vimentin (r'=0.54, p=0.05 and r'=0.61, p=0.02) and intimal N-cadherin (r'=0.62, p=0.03 and r'=0.70, p=0.001) expression respectively; also substantially linked with the intimal thickness (r'=0.52, p=0.04; r'=0.52, p=0.04, respectively). Intimal TGF-?1 expression was strongly correlated with intimal elastin deposition (r'=0.79, p=0.003). Moreover, total TGF-?1 expression significantly affected the DLCO% (r'=-0.61, p=0.03). 

Conclusion:  This is the first comprehensive investigation of the active TGF- ?/Smad-2/3/7 dependent and ?-catenin dependent Wnt signalling pathways driving EndMT, resulting in pulmonary arterial remodelling in IPF patients. EndMT is a promising therapeutic target for vascular remodelling and fibrosis in general for IPF patients.