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All-trans retinoic acid attenuates bleomycin-induced pulmonary fibrosis via downregulating EphA2-EphrinA1 signaling

Authors
 Ah Young Leem  ;  Mi Hwa Shin  ;  Ivor S. Douglas  ;  Joo Han Song  ;  Kyung Soo Chung  ;  Eun Young Kim  ;  Ji Ye Jung  ;  Young Ae Kang  ;  Joon Chang  ;  Young Sam Kim  ;  Moo Suk Park 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.491(3) : 721-726, 2017 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2017
MeSH
Animals ; Cytokines/metabolism* ; Down-Regulation/drug effects ; Ephrin-A1/metabolism* ; Lung/drug effects ; Lung/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis/chemically induced ; Pulmonary Fibrosis/metabolism* ; Pulmonary Fibrosis/prevention & control* ; Receptor, EphA2/metabolism* ; Signal Transduction/drug effects ; Tretinoin/administration & dosage*
Keywords
All-trans retinoic acid ; Bleomycin ; EphA2 ; EphrinA1 ; Pulmonary fibrosis
Abstract
The role of all-trans retinoic acid (ATRA) in pulmonary fibrosis is relatively unknown, although this metabolite modulates cell differentiation, proliferation, and development. We aimed to evaluate the role of ATRA in bleomycin-induced pulmonary fibrosis, and whether the mechanism involves EphA2-EphrinA1 and PI3K-Akt signaling. We evaluated three groups of mice: a control group (intraperitoneal DMSO injection 3 times weekly after PBS instillation), bleomycin group (intraperitoneal DMSO injection 3 times weekly after bleomycin instillation), and bleomycin + ATRA group (intraperitoneal ATRA injection 3 times weekly after bleomycin instillation). The cell counts and protein concentration in the bronchoalveolar lavage fluid (BALF), changes in histopathology, Ashcroft score, hydroxyproline assay, expression of several signal pathway proteins including EphA2-EphrinA1, and PI3K-Akt, and cytokine levels were compared among the groups. We found that bleomycin significantly increased the protein concentration in the BALF, Ashcroft score in lung tissue, and hydroxyproline contents in lung lysates. Furthermore, bleomycin upregulated EphA2, EphrinA1, PI3K 110γ, Akt, IL-6 and TNF-α. However, administration of ATRA attenuated the upregulation of EphA2-EphrinA1 and PI3K-Akt after bleomycin instillation, and decreased pulmonary fibrosis. In addition, ATRA suppressed IL-6 and TNF-α production induced by bleomycin-induced injury. Collectively, these data suggest that ATRA attenuates bleomycin-induced pulmonary fibrosis by regulating EphA2-EphrinA1 and PI3K-Akt signaling.
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X17314808
DOI
10.1016/j.bbrc.2017.07.122
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Young Ae(강영애) ORCID logo https://orcid.org/0000-0002-7783-5271
Kim, Young Sam(김영삼) ORCID logo https://orcid.org/0000-0001-9656-8482
Kim, Eun Young(김은영) ORCID logo https://orcid.org/0000-0002-3281-5744
Park, Moo Suk(박무석) ORCID logo https://orcid.org/0000-0003-0820-7615
Song, Joo Han(송주한)
Leem, Ah Young(임아영) ORCID logo https://orcid.org/0000-0001-5165-3704
Chang, Joon(장준) ORCID logo https://orcid.org/0000-0003-4542-6841
Jung, Kyung Soo(정경수) ORCID logo https://orcid.org/0000-0003-1604-8730
Jung, Ji Ye(정지예) ORCID logo https://orcid.org/0000-0003-1589-4142
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160618
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