Lung fibroblasts express a miR-19a-19b-20a sub-cluster to suppress TGF-β-associated fibroblast activation in murine pulmonary fibrosis. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Souma, Kunihiko; Shichino, Shigeyuki; Hashimoto, Shinichi; Ueha, Satoshi; Tsukui, Tatsuya; Nakajima, Takuya; Suzuki, Hiroshi; Shand, Francis; Inagaki, Yutaka; Nagase, Takahide; Matsushima, Kouji
• Is Part Of: Scientific reports. Volume 8:Issue 1(2018)
• Page Start: 1
• Page End: 14
• Publication Date: 2018-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-018-34839-0
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Lung fibroblasts play a pivotal role in pulmonary fibrosis, a devastating lung disease, by producing extracellular matrix. MicroRNAs (miRNAs) suppress numerous genes post-transcriptionally; however, the roles of miRNAs in activated fibroblasts in fibrotic lungs remain poorly understood. To elucidate these roles, we performed global miRNA-expression profiling of fibroblasts from bleomycin- and silica-induced fibrotic lungs and investigated the functions of miRNAs in activated lung fibroblasts. Clustering analysis of global miRNA-expression data identified miRNA signatures exhibiting increased expression during fibrosis progression. Among these signatures, we found that a miR-19a-19b-20a sub-cluster suppressed TGF-β-induced activation of fibroblastsin vitro . Moreover, to elucidate whether fibroblast-specific intervention against the sub-cluster modulates pathogenic activation of fibroblasts in fibrotic lungs, we intratracheally transferred the sub-cluster-overexpressing fibroblasts into bleomycin-treated lungs. Global transcriptome analysis of the intratracheally transferred fibroblasts revealed that the sub-cluster not only downregulated expression of TGF-β-associated pro-fibrotic genes, includingActa 2, Col1a1, Ctgf, andSerpine1, but also upregulated expression of the anti-fibrotic genesDcn, Igfbp5, andMmp3 in activated lung fibroblasts. Collectively, these findings indicated that upregulation of the miR-19a-19b-20a sub-cluster expression in lung fibroblasts counteracted TGF-β-associated pathogenic activation of fibroblasts in murine pulmonary fibrosis.