Next Article in Journal
Effects of Oral Administration of Chitin Nanofiber on Plasma Metabolites and Gut Microorganisms
Next Article in Special Issue
The Role of HMGB1 Signaling Pathway in the Development and Progression of Hepatocellular Carcinoma: A Review
Previous Article in Journal
GCN5 Potentiates Glioma Proliferation and Invasion via STAT3 and AKT Signaling Pathways
Previous Article in Special Issue
Current Proceedings in the Molecular Dissection of Hepatocellular Adenomas: Review and Hands-on Guide for Diagnosis
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(9), 21911-21930; doi:10.3390/ijms160921911

Ghrelin Attenuates Liver Fibrosis through Regulation of TGF-β1 Expression and Autophagy

1
Department of Gastroenterology and Hepatology, Jinshan Hospital of Fudan University, Shanghai 201508, China
2
Department of Gastroenterology and Hepatology, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Johannes Haybaeck
Received: 1 August 2015 / Revised: 28 August 2015 / Accepted: 31 August 2015 / Published: 10 September 2015
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
View Full-Text   |   Download PDF [13410 KB, uploaded 10 September 2015]   |  

Abstract

Ghrelin is a stomach-derived growth hormone secretagogue that promotes various physiological effects, including energy metabolism and amelioration of inflammation. The purpose of this study was to investigate the protective mechanism of ghrelin against liver fibrosis. Liver fibrosis was induced in C57BL/6 mice by intraperitoneal injection of CCl4 (2.0 mL/kg of 10% CCl4 v/v solution in peanut oil) two times per week for eight weeks. Ghrelin (10 μg/kg) was intraperitoneally injected two times per week for eight weeks. A second murine liver fibrosis model was induced by bile duct ligation (BDL) and concurrent ghrelin administration for four weeks. Hematoxylin eosin (H&E), and Masson’s trichrome were used to detect pathological changes to liver tissue. Western blotting was used to detect protein levels of transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3), I-collage, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, phosphorylated NF-κB (p-NF-κB), and microtubule-associated protein light chain 3 (LC3). In addition, qRT-PCR was used to detect mRNA levels of TGF-β1, I-collage, α-SMA, MMP2, TIMP1 and LC3, while levels of TGF-β1, p-Smad3, I-collage, α-SMA, and LC3 were detected immunohistochemically. Levels of aspartate aminotransferase and alanine aminotransferase were significantly decreased by ghrelin treatment. Ghrelin administration also significantly reduced the extent of pathological changes in both murine liver fibrosis models. Expression levels of I-collage and α-SMA in both models were clearly reduced by ghrelin administration. Furthermore, ghrelin treatment decreased protein expression of TGF-β1 and p-Smad3. The protein levels of NF-κB and LC3 were increased in the CCl4- and BDL-treatment groups but were significantly reduced following ghrelin treatment. In addition, ghrelin inhibited extracellular matrix formation by decreasing NF-κB expression and maintaining the balance between MMP2 and TIMP1. Our results demonstrated that ghrelin attenuates liver fibrosis via inhibition of the TGF-β1/Smad3 and NF-κB signaling pathways, as well as autophagy suppression. View Full-Text
Keywords: ghrelin; CCl4; bile duct ligation; hepatic stellate cells; fibrosis; TGF-β1-Smad; NF-κB; autophagy ghrelin; CCl4; bile duct ligation; hepatic stellate cells; fibrosis; TGF-β1-Smad; NF-κB; autophagy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Mao, Y.; Zhang, S.; Yu, F.; Li, H.; Guo, C.; Fan, X. Ghrelin Attenuates Liver Fibrosis through Regulation of TGF-β1 Expression and Autophagy. Int. J. Mol. Sci. 2015, 16, 21911-21930.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top