miR-29 targets in human fetal lung fibroblast IMR-90 cells

TGF is one of most intensively studied regulators of extracellular matrix formation, and has been implicated in the development of pulmonary fibrosis in different models. However, little is know about the role of miRNAs in TGF mediated fibrogenic gene regulation. By using miRNA qRT-PCR array, we have identified miRNAs whose expression are regulated by TGF in IMR-90 cells. Among those down-regulated miRNAs are miR-29 family members. Knockdown miR-29 in IMR-90 cells results in up-regulation of a large number of extracellular matrix and fibrogenic genes including family members of collagen, laminin, integrin, ADAM and MMP, many of them are predicted or confirmed miR-29 targets. Hierarchichal clustering analysis of mRNA array data revealed that many extracellular matrix and fibrogenic genes up-regulated by TGF in IMR-90 cells, are also up-regulated in miR-29 KD cells. Moreover, the similar set of extracellular matrix and fibrogenic genes is also significantly up-regulated in bleomycin treated mouse lungs. Together, our data strongly suggest that downstream of the TGF, miR-29 is a master modulator of genes involved in extracellular matrix formation and might play a significant role in pulmonary fibrosis.

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Cushing L, Kuang PP, Qian J, Shao F, Wu J, Little F, Thannickal VJ, Cardoso WV, Lü J