Page 36 - N. Metabolism and metabolic diseases

[N. Metabolism and metabolic diseases-20]

The role of pentose phosphate pathway in pulmonary

fibrosis

Seung Hyun Kwon¹, Haksu Kim¹

¹Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, South Korea

Background: Pentose phosphate (PP) pathway is one of the major metabolic pathways associated with glucose
metabolism. Glucose 6-phosphate dehydrogenase (G6PD) is a rate-limiting enzyme of PP pathway. This study aims
to investigate the role of the PP pathway in idiopathic pulmonary fibrosis (IPF). Methods: The metabolites of PP

pathway were analyzed with Agilent GC/MSD system in the human lung tissues. The function of G6PD was evaluated

in vitro and in vivo models of pulmonary fibrosis. Results: The levels of PP pathway metabolites in IPF lung tissues
were significantly elevated than those in control lung tissues. Moreover, protein expression of G6PD was increased
in fibroblasts by TGF-β1 stimulation. 6-aminonicotinamide (6-AN), G6PD inhibitor and G6PD specific siRNA reduced

TGF-induced protein expression levels of fibrotic markers in fibroblasts. In addition, 6-AN decreased the TGF-induced
mRNA and protein expression levels of EMT marker in Beas-2B cells. In study of bleomycin treated mice model, 6-

AN also decreased levels of hydroxyproline in the lung compared to that of control mice. Conclusions: Our data
indicate that inhibition of G6PD may have anti-fibrotic effects on pulmonary fibrosis, suggesting that PP pathway

is implicated as a potential therapeutic target in IPF.