Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2018; 24(30): 3414-3425
Published online Aug 14, 2018. doi: 10.3748/wjg.v24.i30.3414
Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn’s disease intestinal fibrosis
Bo-Lin Yang, Ping Zhu, You-Ran Li, Min-Min Xu, Hao Wang, Li-Chao Qiao, Hai-Xia Xu, Hong-Jin Chen
Bo-Lin Yang, Ping Zhu, You-Ran Li, Min-Min Xu, Hao Wang, Li-Chao Qiao, Hai-Xia Xu, Hong-Jin Chen, Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Author contributions: Yang BL and Chen HJ contributed to the conception and design of the study, acquisition, analysis and interpretation of data; all authors drafted the article and made critical revisions, and approved the final version of the article to be published.
Supported by the Natural Science Foundation of Jiangsu Province, China, No. BK2016157; the National Natural Science Foundation of China, No. 81673973; Phase II Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, No. 035062002003; and Developing Program for High-level Academic Talent in Jiangsu Hospital of TCM, No. y2018rc16.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hong-Jin Chen, MD, Chief Doctor, Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Hanzhong 155 Rd, Nanjing 210029, Jiangsu Province, China. 260789@njucm.edu.cn
Telephone: +86-13851887158
Received: May 10, 2018
Peer-review started: May 10, 2018
First decision: June 11, 2018
Revised: June 27, 2018
Accepted: June 28, 2018
Article in press: June 28, 2018
Published online: August 14, 2018
Processing time: 95 Days and 17.6 Hours
Abstract
AIM

To explore the role and mechanism of total flavone of Abelmoschus manihot (TFA) on epithelial-mesenchymal transition (EMT) progress of Crohn’s disease (CD) intestinal fibrosis.

METHODS

First, CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial (IEC-6) cells and select the optimal concentrations of TFA for our further studies. Then cell morphology, wound healing and transwell assays were performed to examine the effect of TFA on morphology, migration and invasion of IEC-6 cells treated with TGF-β1. In addition, immunofluorescence, real-time PCR analysis (qRT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress. Moreover, western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways. Further, the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by qRT-PCR, western blotting, morphology, wound healing and transwell assays.

RESULTS

In this study, TFA promoted transforming growth factor-β1 (TGF-β1)-induced (IEC-6) morphological change, migration and invasion, and increased the expression of epithelial markers and reduced the levels of mesenchymal markers, along with the inactivation of Smad and MAPK signaling pathways. Moreover, we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 cells. Importantly, co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of them.

CONCLUSION

These findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

Keywords: Crohn’s disease; Intestinal fibrosis; Epithelial-to-mesenchymal transition; Total flavone of Abelmoschus manihot; Transforming growth factor-β1/Smad signaling; Transforming growth factor-β1/non-Smad signaling

Core tip: Regulating transforming growth factor-β (TGF-β) and its downstream signaling pathways, mediating the epithelial-mesenchymal transition (EMT) process and restoring the biological function of abnormally activated intestinal fibroblasts, may be an important way to seek drug therapy for Crohn’s disease (CD) intestinal fibrosis. Total flavone of Abelmoschus manihot (TFA) can inhibit TGF-β1-induced morphological change, migration, invasion of rat intestinal epithelial cells, and promote induction of EMT partially by inhibiting TGF-β1-activated Smad and non-Smad signaling pathways. Therefore, TFA is expected to advance as a new therapy to treat CD intestinal fibrosis, and its continued advancement may open the door to a new class of treatment for CD intestinal fibrosis.