miR-130b-3p Modulates Epithelial-Mesenchymal Crosstalk in Lung Fibrosis by Targeting IGF-1
Authors: Huaping Dai
Dong Leng
Chen Wang
Dianhua Jiang
Jing Geng
Shuhong Li
Xuefeng Xu
Xiaoxi Huang
Jiurong Liang
Dingyuan Jiang
Journal: PLoS ONE (2016)
Discipline: Multidisciplinary
Keywords: Idiopathic pulmonary fibrosis; microRNAs; miR-130b-3p; lung fibrosis; Affymetrix microarray
Affiliations: Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital-Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, P.R. China., National Clinical Research Centre for Respiratory Medicine, Beijing Hospital, Beijing 100730, P.R. China., Department of Medical Research, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China., Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China., Department of Medicine Pulmonary Division and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States of America., Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, 100029, P.R. China.

Abstract:  Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and usually lethal fibrotic lung disease with largely unknown etiology and pathogenesis. Evidence suggests microRNAs (miRNA) contribute to pathogenesis of IPF. In this study, we sought to identify miRNA expression signatures and determine the role of miR-130b-3p in lung fibrosis. The miRNA expression profile of the lungs from patients with IPF and normal donors was determined by Affymetrix microarray, and transcriptome with Affymetrix array. The functions and signal pathways as well as miRNA-mRNA networks were established by bioinformatics analysis. Luciferase assays and ELISA were used to confirm the miRNA target gene. The effect of miRNA-transfected epithelium on fibroblast activities was assessed using a co-culture system. The fibroblast activities were determined by qRT-PCR, western blotting, Transwell and BrdU assays. Seven miRNAs were significantly decreased in IPF lungs, with miR-130b-3p being the highest in the miRNA-mRNA network. Insulin-like growth factor (IGF-1) was a target gene of miR-130b-3p in the epithelium. miR-130b-3p inhibition in the epithelium induced collagen I expression and enhanced the proliferation and migration ability of fibroblast in co-culture systems, which mimicked the functions of exogenous IGF-1 on fibroblasts. Neutralizing IGF-1 with an antibody significantly reduced the modulatory effects of miR-130b-3p inhibitor-transfected epithelium on the activation of fibroblasts. Our results show that miR-130b-3p was downregulated in IPF lungs. miR-130b-3p downregulation contributed to the activation of fibroblasts and the dysregulated epithelial-mesenchymal crosstalk by promoting IGF-1 secretion from lung epithelium, suggesting a key regulatory role for this miRNA in preventing lung fibrosis. 

Retracted: No

PubPeer comments:
 The actin control in Fig 5.D is identical with the actin control in Fig 7.A, as shown below marked with red box: ![file] ![file] , 
 This is the first author of the study. We thank the reader noting that Figure 7A and Figure 5D contained the same u03b2-actin images. Figure 7A mainly shows collagen I expression of MRC5 induced by miR-130b-3p inhibitor was significantly reduced by human IGF-1 antibody treatment. Unfortunately, in the process of Figure production and integration, the image in Figure 7A was used incorrectly. The authors have contacted the Editor in Chief of PLoS ONE for corrigendum and have provided an updated version of Figure 7 and Figure S3C. Although this error does not affect the understanding on the function of miR-130b-3p in lung fibrosis, we deeply regret the error. ![file] , 
 #2 Thanks for the reply. Could the author please explain why the newly provided data so blurry, compare to the collagen image? Could the authors show the full raw data contain both the collagen and b-actin to prove that they are from the same experiments? ,