Browsing by Subject "Pulmonary Fibrosis"

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    Periostin, a matricellular protein, plays a role in the induction of chemokines in pulmonary fibrosis
    (American Thoracic Society, 2012-05) Uchida, Masaru; Shiraishi, Hiroshi; Ohta, Shoichiro; Arima, Kazuhiko; Taniguchi, Kazuto; Suzuki, Shoichi; Okamoto, Masaki; Ahlfeld, Shawn K.; Ohshima, Koichi; Kato, Seiya; Toda, Shuji; Sagara, Hironori; Aizawa, Hisamichi; Hoshino, Tomoaki; Conway, Simon J.; Hayashi, Shinichiro; Izuhara, Kenji; Department of Pediatrics, IU School of Medicine
    Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal form of interstitial lung disease (ILD). The precise molecular mechanisms of IPF remain poorly understood. However, analyses of mice receiving bleomycin (BLM) as a model of IPF established the importance of preceding inflammation for the formation of fibrosis. Periostin is a recently characterized matricellular protein involved in modulating cell functions. We recently found that periostin is highly expressed in the lung tissue of patients with IPF, suggesting that it may play a role in the process of pulmonary fibrosis. To explore this possibility, we administered BLM to periostin-deficient mice, and they subsequently showed a reduction of pulmonary fibrosis. We next determined whether this result was caused by a decrease in the preceding recruitment of neutrophils and macrophages in the lungs because of the lower production of chemokines and proinflammatory cytokines. We performed an in vitro analysis of chemokine production in lung fibroblasts, which indicated that periostin-deficient fibroblasts produced few or no chemokines in response to TNF-α compared with control samples, at least partly explaining the lack of inflammatory response and, therefore, fibrosis after BLM administration to periostin-deficient mice. In addition, we confirmed that periostin is highly expressed in the lung tissue of chemotherapeutic-agent-induced ILD as well as of patients with IPF. Taking these results together, we conclude that periostin plays a unique role as an inducer of chemokines to recruit neutrophils and macrophages important in the process of pulmonary fibrosis in BLM-administered model mice. Our results suggest a therapeutic potential for periostin in IPF and drug-induced ILD.
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    Regulation of Collagen V Expression and Epithelial-Mesenchymal Transition by miR-185 and miR-186 during Idiopathic Pulmonary Fibrosis
    (Elsevier, 2016-09) Lei, Guang-Sheng; Kline, Hannah L.; Lee, Chao-Hung; Wilkes, David S.; Zhang, Chen; Pathology and Laboratory Medicine, School of Medicine
    Idiopathic pulmonary fibrosis is a devastating disease, with no good diagnostic biomarker and limited treatment options. Previous studies suggest that collagen V overexpression and collagen V–mediated immune response play roles in the pathogenesis of idiopathic pulmonary fibrosis. This study aimed to identify dysregulated miRNA-related collagen V overexpression during idiopathic pulmonary fibrosis. We found that the expression levels of miR-185 and miR-186 were decreased in the lungs of idiopathic pulmonary fibrosis patients. The levels of miR-185 and miR-186 were not correlated with disease severity of idiopathic pulmonary fibrosis. The direct regulation of COL5A1 by miR-185 and miR-186 was confirmed by a luciferase reporter assay. Furthermore, mimics of miR-185 and miR-186 blocked transforming growth factor-β–induced collagen V overexpression and alleviated transforming growth factor-β–induced epithelial-mesenchymal transition in A549 cells and HCC827 cells. Our findings suggest that attenuated expression of miR-185 and miR-186 may be responsible for collagen V overexpression during idiopathic pulmonary fibrosis, and these miRNAs may serve as pathogenesis-related biomarkers and treatment targets.