RATIONALE: Increased abundance and stiffness of the extracellular matrix, in 
particular collagens, is a hallmark of idiopathic pulmonary fibrosis (IPF). 
FK506-binding protein 10 (FKBP10) is a collagen chaperone, mutations of which 
have been indicated in the reduction of extracellular matrix stiffness (e.g., in 
osteogenesis imperfecta).
OBJECTIVES: To assess the expression and function of FKBP10 in IPF.
METHODS: We assessed FKBP10 expression in bleomycin-induced lung fibrosis (using 
quantitative reverse transcriptase-polymerase chain reaction, Western blot, and 
immunofluorescence), analyzed microarray data from 99 patients with IPF and 43 
control subjects from a U.S. cohort, and performed Western blot analysis from 6 
patients with IPF and 5 control subjects from a German cohort. Subcellular 
localization of FKBP10 was assessed by immunofluorescent stainings. The 
expression and function of FKBP10, as well as its regulation by endoplasmic 
reticulum stress or transforming growth factor-β1, was analyzed by small 
interfering RNA-mediated loss-of-function experiments, quantitative reverse 
transcriptase-polymerase chain reaction, Western blot, and quantification of 
secreted collagens in the lung and in primary human lung fibroblasts (phLF). 
Effects on collagen secretion were compared with those of the drugs nintedanib 
and pirfenidone, recently approved for IPF.
MEASUREMENTS AND MAIN RESULTS: FKBP10 expression was up-regulated in 
bleomycin-induced lung fibrosis and IPF. Immunofluorescent stainings 
demonstrated localization to interstitial (myo)fibroblasts and CD68(+) 
macrophages. Transforming growth factor-β1, but not endoplasmic reticulum 
stress, induced FKBP10 expression in phLF. The small interfering RNA-mediated 
knockdown of FKBP10 attenuated expression of profibrotic mediators and 
effectors, including collagens I and V and α-smooth muscle actin, on the 
transcript and protein level. Importantly, loss of FKBP10 expression 
significantly suppressed collagen secretion by phLF.
CONCLUSIONS: FKBP10 might be a novel drug target for IPF.