MiR-185 / AKT and miR-29a / Collagen 1a pathways are activated in IPF BAL cells
File(s)
Author(s)
Type
Journal Article
Abstract
MicroRNA signatures of BAL cells and alveolar macrophages are currently lacking in IPF. Here we sought to investigate the expression of fibrosis-related microRNAs in the cellular component of the BAL in IPF. We thus focused on microRNAs previously associated with fibrosis (miR-29a, miR-29b, miR-29c, let-7d, and miR-21) and rapid IPF progression (miR-185, miR-210, miR-302c-3p miR-376c and miR-423-5p). Among the tested microRNAs miR-29a and miR-185 were found significantly downregulated in IPF while miR-302c-3p and miR-376c were not expressed by BAL cells. Importantly, the downregulation of miR-29a inversely correlated with the significantly increased levels of COL1A1 mRNA in IPF BAL cells. Collagen 1 a was found mainly overexpressed in alveolar macrophages and not other cell types of the BAL by immunofluorescence. In view of the downregulation of miR-185, we tested the response of THP-1 macrophages to profibrotic cytokine TGFb and observed the downregulation of miR-185. Conversely, proinflammatory stimulation lead to miR-185 upregulation. Upon examination of the mRNA levels of known miR-185 targets AKT1, DNMT1 and HMGA2, no significant correlations were observed in the BAL cells. However, increased levels of total AKT and AKTser473 phosphorylation were observed in the IPF BAL cells. Furthermore, miR-185 inhibition in THP-1 macrophages resulted in significant increase of AKTser473 phosphorylation. Our study highlights the importance of BAL microRNA signatures in IPF and identifies significant differences in miR-185/AKT and miR-29a/collagen axes in the BAL cells of IPF patients.
Date Issued
2016-10-18
Date Acceptance
2016-10-04
Citation
Oncotarget, 2016, 7 (46), pp.74569-74581
ISSN
1949-2553
Publisher
Impact Journals
Start Page
74569
End Page
74581
Journal / Book Title
Oncotarget
Volume
7
Issue
46
Copyright Statement
© 2016 The Authors. This is an open access article under a CC-BY Licence (https://creativecommons.org/licenses/by/3.0/)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000389632800013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
IPF
microRNA
bronchoalveolar lavage fluid
collagen
AKT
Immunology and Microbiology Section
Immune response
Immunity
IDIOPATHIC PULMONARY-FIBROSIS
EOSINOPHIL ACTIVATION
LUNG FIBROBLASTS
MACROPHAGES
PROGRESSION
ALVEOLITIS
MICRORNAS
CCL18
MODEL
FLUID
Publication Status
Published