SMTP-44D, a soluble epoxide hydrolase inhibitor, attenuated the progression of pulmonary fibrosis in vivo and in vitro.

<bold>Background:</bold> SMTP-44D is one of the Stachybotrys microspora triprenyl phenol (SMTP) homologues extracted from the filamentous fungus <italic>Stachybotrys microspora</italic>. SMTP-44D inhibits the activity of soluble epoxide hydrolase (sEH) and suppresses the hydrolysis of epoxyeicosatrienoic acids (EETs). Although EETs are known to have anti-fibrotic effect, the efficacy of SMTP-44D on pulmonary fibrosis is unknown. In this study, we evaluated the antifibrotic effect of SMTP-44D on experimental pulmonary fibrosis <italic>in vivo</italic> and <italic>in vitro</italic>. <bold>Methods:</bold> The experimental lung fibrosis was induced in mice by intratracheal administration of bleomycin. Mice were received intraperitoneal administration of SMTP-44D three times per week. Lung tissues harvested on day 21 used for histopathological analysis and quantified collagen assay. The expression of pro-fibrotic markers in lung fibroblast was determined by a quantitative PCR. A ³H-thymidine incorporation assay was used to evaluate the proliferation of lung fibroblasts. <bold>Results:</bold> <italic>In vivo</italic>, histological analysis and collagen assay showed that SMTP-44D significantly attenuated lung fibrosis. <italic>In vitro</italic>, SMTP-44D, as well as EETs, reduced the expression of COL1A1 and ACTA2 induced by TGF-b1 in lung fibroblasts. SMTP-44D suppressed fibroblast proliferation induced by PDGF-BB and FGF2 while EETs did not either. <bold>Conclusions:</bold> SMTP-44D attenuates pulmonary fibrosis in part by a mechanism different from EETs upregulation. SMTP-44D is a potentially therapeutic candidate for pulmonary fibrosis.