Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a poor prognosis. Thus, to discover drugs providing new therapeutic options for patients with IPF is necessary. Myofibroblasts (MyoFs) that produce abundant extracellular matrix play key roles in the development of IPF. Although the pathogenic MyoFs mainly differentiated from resident fibroblasts have been considered as the irreversible phenotype, it has been recently reported that some agents dedifferentiating MyoFs into fibroblasts can attenuate bleomycin-induced lung fibrosis in mice. This finding tempts us to consider induction of MyoF dedifferentiation as a new beneficial strategy for patients with IPF. However, the detailed mechanisms of MyoF dedifferentiation are still unknown.
We have already established several strains of primary cultured MyoF-like cells (MyoLCs) from the fibrotic lungs of patients who underwent lung transplantation as a result of severe fibrosis. Employing the MyoLCs (S100A4^-α-SMA^highED-A-fibronectin⁺: > 90%) as an in vitro screening system, we found that JQ1, a bromodomain inhibitor could induce MyoF dedifferentiation associated with the downregulation in expression of α-SMA and ED-A fibronectin. Then, we comprehensively investigated the change in expression of microRNAs in JQ1-treted MyoLCs. Based on these results, we will discuss the molecular mechanisms of MyoF dedifferentiation.