Page 252 - ebook

[D. Medicine/Translational Research] D-10

Inhibition of glucose 6-phosphate dehydrogenase alleviates

pulmonary fibrosis

Hak Su Kim¹

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

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). The metabolites of PP pathway were analyzed with
Agilent 7890/5975 GC/MSD system and HP-5 MS column in the human lung tissues. The function of G6PD was

evaluated in vitro and in vivo models of pulmonary fibrosis. 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 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 factor in Beas-2b cells. In bleomycin treated mice, 6-AN also decreased levels of
hydroxyproline in the lung compared to that of control mice. 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.