Tags

Type your tag names separated by a space and hit enter

Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial-mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis.
Lab Invest. 2017 03; 97(3):232-242.LI

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause. IPF has a distinct histopathological pattern of usual interstitial pneumonia in which fibroblastic foci (FF) represent the leading edge of fibrotic destruction of the lung. Currently there are three major hypotheses for how FF are generated: (1) from resident fibroblasts, (2) from bone marrow-derived progenitors of fibroblasts, and (3) from alveolar epithelial cells that have undergone epithelial-mesenchymal transition (EMT). We found that FF dissociated capillary vessels from the alveolar epithelia, the basement membranes of which are fused in normal physiological conditions, and pushed the capillaries and elastic fibers down ~100 μm below the alveolar epithelia. Furthermore, the alveolar epithelial cells covering the FF exhibited a partial EMT phenotype. In addition, normal human alveolar epithelial cells in vitro underwent dynamic EMT in response to transforming growth factor-β signaling within 72 h. Because it seems that resident fibroblasts or bone marrow-derived cells cannot easily infiltrate and form FF between the alveolar epithelia and capillaries in tight contact with each other, FF are more likely to be derived from the epithelial-to-mesenchymal transitioned alveolar epithelia located over them. Moreover, histology and immunohistochemistry suggested that the FF formed in the lung parenchyma disrupt blood flow to the alveolar septa, thus destroying them. Consequently, collapse of the alveolar septa is likely to be the first step toward honeycombing in the lung during late stage IPF. On the basis of these findings, inhibition of transforming growth factor-β signaling, which can suppress EMT of the alveolar epithelial cells in vitro, is a potential strategy for treating IPF.

Authors+Show Affiliations

Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Thoracic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Thoracic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Pathology, Jichi Medical University School of Medicine, Tochigi, Japan.Department of Thoracic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27941755

Citation

Yamaguchi, Miki, et al. "Fibroblastic Foci, Covered With Alveolar Epithelia Exhibiting Epithelial-mesenchymal Transition, Destroy Alveolar Septa By Disrupting Blood Flow in Idiopathic Pulmonary Fibrosis." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 97, no. 3, 2017, pp. 232-242.
Yamaguchi M, Hirai S, Tanaka Y, et al. Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial-mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis. Lab Invest. 2017;97(3):232-242.
Yamaguchi, M., Hirai, S., Tanaka, Y., Sumi, T., Miyajima, M., Mishina, T., Yamada, G., Otsuka, M., Hasegawa, T., Kojima, T., Niki, T., Watanabe, A., Takahashi, H., & Sakuma, Y. (2017). Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial-mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis. Laboratory Investigation; a Journal of Technical Methods and Pathology, 97(3), 232-242. https://doi.org/10.1038/labinvest.2016.135
Yamaguchi M, et al. Fibroblastic Foci, Covered With Alveolar Epithelia Exhibiting Epithelial-mesenchymal Transition, Destroy Alveolar Septa By Disrupting Blood Flow in Idiopathic Pulmonary Fibrosis. Lab Invest. 2017;97(3):232-242. PubMed PMID: 27941755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial-mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis. AU - Yamaguchi,Miki, AU - Hirai,Sachie, AU - Tanaka,Yusuke, AU - Sumi,Toshiyuki, AU - Miyajima,Masahiro, AU - Mishina,Taijiro, AU - Yamada,Gen, AU - Otsuka,Mitsuo, AU - Hasegawa,Tadashi, AU - Kojima,Takashi, AU - Niki,Toshiro, AU - Watanabe,Atsushi, AU - Takahashi,Hiroki, AU - Sakuma,Yuji, Y1 - 2016/12/12/ PY - 2016/08/10/received PY - 2016/10/28/revised PY - 2016/11/10/accepted PY - 2016/12/13/pubmed PY - 2017/6/28/medline PY - 2016/12/13/entrez SP - 232 EP - 242 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab Invest VL - 97 IS - 3 N2 - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause. IPF has a distinct histopathological pattern of usual interstitial pneumonia in which fibroblastic foci (FF) represent the leading edge of fibrotic destruction of the lung. Currently there are three major hypotheses for how FF are generated: (1) from resident fibroblasts, (2) from bone marrow-derived progenitors of fibroblasts, and (3) from alveolar epithelial cells that have undergone epithelial-mesenchymal transition (EMT). We found that FF dissociated capillary vessels from the alveolar epithelia, the basement membranes of which are fused in normal physiological conditions, and pushed the capillaries and elastic fibers down ~100 μm below the alveolar epithelia. Furthermore, the alveolar epithelial cells covering the FF exhibited a partial EMT phenotype. In addition, normal human alveolar epithelial cells in vitro underwent dynamic EMT in response to transforming growth factor-β signaling within 72 h. Because it seems that resident fibroblasts or bone marrow-derived cells cannot easily infiltrate and form FF between the alveolar epithelia and capillaries in tight contact with each other, FF are more likely to be derived from the epithelial-to-mesenchymal transitioned alveolar epithelia located over them. Moreover, histology and immunohistochemistry suggested that the FF formed in the lung parenchyma disrupt blood flow to the alveolar septa, thus destroying them. Consequently, collapse of the alveolar septa is likely to be the first step toward honeycombing in the lung during late stage IPF. On the basis of these findings, inhibition of transforming growth factor-β signaling, which can suppress EMT of the alveolar epithelial cells in vitro, is a potential strategy for treating IPF. SN - 1530-0307 UR - https://www.unboundmedicine.com/medline/citation/27941755/Fibroblastic_foci_covered_with_alveolar_epithelia_exhibiting_epithelial_mesenchymal_transition_destroy_alveolar_septa_by_disrupting_blood_flow_in_idiopathic_pulmonary_fibrosis_ L2 - https://doi.org/10.1038/labinvest.2016.135 DB - PRIME DP - Unbound Medicine ER -