INTRODUCTION: Novel treatments for idiopathic pulmonary fibrosis (IPF) are needed urgently. A better understanding of the molecular pathways activated by TGFβ1 in human lung tissue may facilitate the development of more effective anti-fibrotic medications. This study utilized proteomic analysis to test the hypothesis that TGFβ1 induces pro-fibrotic effects on human lung parenchyma proteome, and to evaluate the viability of this model for testing novel therapeutic targets. METHODS: Non-fibrotic human lung parenchymal tissue from 11 patients was cultured for 7 days in serum-free (SF) media supplemented with TGFβ1 (10 ng/mL) or vehicle control, and the putative antifibrotic K RESULTS: TGFβ1 stimulation for 7 days induced a strong fibrotic protein response relevant to IPF pathology. A total of 2391 proteins were quantified, 306 upregulated and 285 downregulated (FDR-adjusted p-value<
0.05). Of these, 118 were upregulated and 28 downregulated at log CONCLUSION: A pro-fibrotic proteome is induced in human lung parenchyma exposed to TGFβ1, sensitive to pharmacological intervention. This approach has the potential to enhance therapeutic drug screening for IPF treatment.