目的 Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and highly lethal fibrotic lung disease with unknown cause or cure.Although some microRNAs (miRNAs) have been confirmed the contribution to the pathophysiological processes of IPF, the roles of miRNAs and intrinsic links between them in fibrotic lung diseases are not yet well understood.方法 We induced pulmonary fibrosis by intratracheally injection of Bleomycin (BLM).Massons Trichrome stained method was used to evaluate the development of fibrosis and the content of collagen is quantified by Sircol Collagen Assay Kit or Hydroxyproline Assay Kit.In cultured A549 cells and HEK-293 cells, synthesized miR-26a, both with its antisense inhibitor oligonucleotide (AMO-26a) and negative control (NC) were transfected or cotransfected with lipofectamine 2000.Western blot was used to examine TGFβ1, Lin28B, E-Cadherin expression and real-time PCR was used to detect miR-26a, let-7d, CollagenⅠ, CollagenⅢ at mRNA levels.结果 In our study, we identified and constructed a regulation network of differentially expressed IPF miRNAs and EMT genes.Additionally, we found the downregulation of miR-26a and upregulation of Lin28B in mice with experimental pulmonary fibrosis.Furthermore, we found that Lin28B could induce the process of epithelial-mesenchymal transition (EMT) by inhibiting let-7d, whereas inhibition of Lin28B mitigated TGF-β1-induced fibrogenesis and attenuated EMT in both cultured A549 cells and MLE-12 cells.In addition, inhibition of miR-26a resulted in lung epithelial cells transforming into myofibroblasts in vitro and in vivo, whereas forced expression of miR-26a alleviated TGF-b1- and BLM-induced EMT in A549 cells and in mice, respectively.More importantly, over-expression of miR-26a could simultaneously enhance the expression of let-7d in A549 cells, and further study confirmed that Lin28B was one of the direct targets of miR-26a, which mediates, at least in part, the regulatory effects of miR-26a on the biogenesis of let-7d.Finally, we constructed a regulatory network among miRNAs involved in the progression of IPF. 结论 Taken together, our study deciphered the essential role of miR-26a and Lin28B in the pathogenesis of EMT and pulmonary fibrosis, and unraveled a novel mechanism that miR-26a is a modulator of let-7d.This study suggests that miR-26a may be a potential therapeutic target for IPF, and also defines the miRNAs network involved in IPF, which may have implications for developing new strategies for pulmonary fibrosis.