Next Article in Journal
A Quantitative Structure-Property Relationship (QSPR) Study of Aliphatic Alcohols by the Method of Dividing the Molecular Structure into Substructure
Previous Article in Journal
Nutritional Deficiencies and Phospholipid Metabolism
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2011, 12(4), 2434-2447; doi:10.3390/ijms12042434

Reactive Oxygen Species Released from Hypoxic Hepatocytes Regulates MMP-2 Expression in Hepatic Stellate Cells

1
Department of Pathology, School of Medicine, Southeast University, Nanjing 210009, China
2
Department of Pathology, Jiangsu Province Hospital of TCM, Nanjing 210029, China
3
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, K1A 0R6, Canada
*
Author to whom correspondence should be addressed.
Received: 7 March 2011 / Revised: 31 March 2011 / Accepted: 2 April 2011 / Published: 7 April 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
View Full-Text   |   Download PDF [594 KB, uploaded 19 June 2014]   |  

Abstract

Hypoxia is a common environmental stress factor and is associated with fibrogenesis. Matrix metalloproteinase-2 (MMP-2), produced by hepatic stellate cells (HSCs), plays an important role in liver fibrogenesis. However, inconsistent results have been reported on the impact of hypoxia on MMP-2 expression and activity in HSCs. We speculated that cell–cell interaction is involved in the regulation of MMP-2 expression and activity at low oxygen level in vivo. Therefore, in this report we investigated the mechanism by which hypoxic hepatocytes regulates MMP-2 expression in HSCs. Our results showed that the conditioned medium from hypoxia-treated rat hepatocytes strongly induced the expression of MMP-2 mRNA and protein in rat HSC-T6 cells. Reduced glutathione neutralized ROS released from hypoxic hepatocytes, leading to reduced MMP-2 expression in HSC-T6 cells. In addition, phospho-IκB-α protein level was increased in HSC-T6 cells treated with hypoxia conditioned medium, and NF-κB signaling inhibitor inhibited MMP-2 expression in HSC-T6 cells. Taken together, our data suggest that ROS is an important factor released by hypoxic hepatocytes to regulate MMP-2 expression in HSCs, and NF-κB signaling is crucially involved in ROS-induced MMP-2 expression in HSCs. Our findings suggest that strategies aimed at antagonizing the generation of ROS in hypoxic hepatocytes and inhibiting NF-κB signaling in HSCs may represent novel therapeutic options for liver fibrosis.
Keywords: hypoxia; hepatocyte; hepatic stellate cells; liver fibrosis; reactive oxygen species hypoxia; hepatocyte; hepatic stellate cells; liver fibrosis; reactive oxygen species
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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

Li, J.; Fan, R.; Zhao, S.; Liu, L.; Guo, S.; Wu, N.; Zhang, W.; Chen, P. Reactive Oxygen Species Released from Hypoxic Hepatocytes Regulates MMP-2 Expression in Hepatic Stellate Cells. Int. J. Mol. Sci. 2011, 12, 2434-2447.

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