Kinase inhibitors fail to induce mesenchymal-epithelial transition in fibroblasts from fibrotic lung tissue
Authors: Xuan Wan
Huaping Dai
Chen Wang
Fei Li
Jing Geng
Xuefeng Xu
Journal: International journal of molecular medicine (2013)
Discipline: CLINICAL MEDICINE
Keywords: Epithelial-mesenchymal transition; EMT; Idiopathic pulmonary fibrosis; IPF; Mesenchymal-epithelial transition
Affiliations: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.

Abstract:  Epithelial-mesenchymal transition (EMT) has been considered to be involved in idiopathic pulmonary fibrosis (IPF). However, the EMT process in vivo is much more complex and controversial. Studies regarding the opposite process, mesenchymal-epithelial transition (MET) in fibroblasts, are limited. Therefore, the aim of this study was to verify the involvement of the transforming growth factor (TGF)-β1-dependent EMT network in the process of pulmonary fibrosis and to explore the possibility of MET. Fibrotic lung tissues were obtained from patients with IPF with histological evidence of usual interstitial pneumonia at the time of surgical lung biopsy. For the controls, histologically normal lung tissues were obtained from patients with primary spontaneous pneumothorax at the time of thoracoscopy with stapling of any air leaks. Real-time RT-PCR and western blot analysis revealed that the mRNA and protein levels of TGF-β1, TGF-β1 receptor type I/II/III (TβRI/II/III), Smad2/3/4 and Snail1/2 were significantly upregulated in the fibrotic lung tissue. Inhibitors of various kinases implicated in EMT, including TGF-β1/Smad, Rho kinase (ROCK), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH-terminal kinase (JNK) were used to determine the MET potential in fibroblasts from fibrotic lung tissue. Western blot analysis or indirect immunofluorescence staining revealed that Smad inhibitor, as well as other kinase inhibitors failed to induce the MET process, determined by cellular morphology and protein markers. Our data suggest that the MET process may not be the exact reversal of EMT. In addition to using kinase inhibitors, other intervention measures should be used to explore the possibility of the MET process in fibroblasts from fibrotic lung tissue. 

Retracted: No

PubPeer comments:
 Figure 4A and Figure 5A showed identical control figure, could the author please explain? ![file] ![file] , 
 This is the first author (Xuefeng Xu, on behalf of Huaping Dai, the Corresponding author) of the study. We thank the reader noting that Figure 4A(Figure 3A, actually) and Figure 5A contained the same light microscope images. Figure 3A mainly shows the cell morphology of primary cultured human lung fibroblasts. Unfortunately, in the process of figure production and integration, the image in Figure 5A was used incorrectly and repeatedly. The authors have contacted the Editor in Chief of International Journal of Molecular Medicine for corrigendum and have provided an updated version of Figure 3. Although this error does not affect the understanding on the morphology of human lung fibroblasts, we deeply regret the error. ![file] ,