MicroRNAs (miRNA) are small regulatory RNAs that control gene expression by 
translational suppression and destabilization of target mRNAs. There is 
increasing evidence that miRNAs regulate genes associated with fibrosis in 
organs, such as the heart, kidney, liver, and the lung. In a large-scale 
screening for miRNAs potentially involved in bleomycin-induced fibrosis, we 
found expression of miR-29 family members significantly reduced in fibrotic 
lungs. Analysis of normal lungs showed the presence of miR-29 in subsets of 
interstitial cells of the alveolar wall, pleura, and at the entrance of the 
alveolar duct, known sites of pulmonary fibrosis. miR-29 levels inversely 
correlated with the expression levels of profibrotic target genes and the 
severity of the fibrosis. To study the impact of miR-29 down-regulation in the 
lung interstitium, we characterized gene expression profiles of human fetal lung 
fibroblast IMR-90 cells in which endogenous miR-29 was knocked down. This 
confirmed the derepression of reported miR-29 targets, including several 
collagens, but also revealed up-regulation of a large number of previously 
unrecognized extracellular matrix-associated and remodeling genes. Moreover, we 
found that miR-29 is suppressed by transforming growth factor (TGF)-β1 in these 
cells, and that many fibrosis-associated genes up-regulated by TGF-β1 are 
derepressed by miR-29 knockdown. Interestingly, a comparison of TGF-β1 and 
miR-29 targets revealed that miR-29 controls an additional subset of 
fibrosis-related genes, including laminins and integrins, independent of TGF-β1. 
Together, these strongly suggest a role of miR-29 in the pathogenesis of 
pulmonary fibrosis. miR-29 may be a potential new therapeutic target for this 
disease.