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Liver Center - Anping Chen, PhD

Anping Chen, PhD


To elucidate molecular mechanisms underlying hepatic fibrogenesis, and to search for natural anti-fibrotic agents for the prevention and treatment of this disease.


Hepatic fibrosis is the scarring response of the liver to chronic hepatic injury, stemming from viral infection, drug hepatitis or sustained alcohol abuse. The latter stands for approximately 50% of death due to cirrhosis in Western societies. Hepatic fibrosis progresses, if unchecked, to cirrhosis. Hepatic stellate cells (HSC), previously called fat- or vitamin A-storing cells, or Ito cells, are the most relevant cell type and the primary source of the excessive production of extracellular matrix (ECM) during hepatic fibrogenesis. HSC normally reside in the space of Disse in a quiescent, non-proliferative state. During hepatic injury, quiescent HSC undergo profound phenotypic changes, including enhanced cell proliferation, de novo expression of  smooth muscle actin ( SMA), and excessive production of ECM. This process is called HSC activation. Culturing quiescent HSC on plastic plates causes spontaneous activation, mimicking the process seen in vivo, which provides a good model for elucidating underlying mechanisms of HSC activation and for studying possible therapeutic intervention of the process. Compelling evidence has shown that HSC activation and hepatic fibrogenesis is induced by oxidative stress. HSC activation, characterized by enhanced cell growth and over-production of ECM, is triggered by the release of mitogenic platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibrogenic transforming growth factor-beta1 (TGF-ß1) from Kupffer cells and activated HSC. This process is coupled with the sequential up-expression of PDGF-beta receptor (PDGF-ßR), type I & II receptors for TGF-ß, epidermal growth factor receptor (EGFR) and connective tissue growth factor (CTGF). The latter mediates TGF ß-induced ECM production. In addition, HSC activation coincides with a dramatic reduction in the peroxisome proliferator-activated receptor-gamma (PPAR) and an increase in PPARß/. Inflammation is a key event in the stimulation of HSC activation and hepatic fibrosis. While PDGF is the most potent mitogen for HSC proliferation, TGF ß is the most powerful inducer for HSC activation and ECM production. Activation of PPAR by its exogenous agonists inhibits HSC activation in vitro and liver fibrogenesis in vivo.

Curcumin is the yellow pigment of turmeric in curry. Besides its role as a dietary spice, turmeric has been used for centuries as an anti-inflammatory remedy in Chinese medicine. Curcumin has received attention as a promising dietary supplement for cancer prevention and liver protection. It is widely accepted that HSC activation and hepatic fibrogenesis is caused by oxidative stress. Although the antioxidant vitamin E inhibits HSC activation and hepatic fibrogenesis, currently well-known antioxidants are not very effective in protecting the liver from fibrogenesis. Curcumin is a potent antioxidant. It attenuates oxidative stress by scavenging free radicals and reducing lipid peroxidation, which might be mainly because of its capability to affect antioxidant enzyme systems. This unique feature might allow curcumin to succeed where other "regular" antioxidants have failed to inhibit hepatic fibrogenesis. We recently reported that curcumin significantly inhibited HSC activation in vitro by reducing cell growth and suppressing ECM gene expression [Xu J., Fu Y. & Chen A. (2003) Am J Physiol Gastrointest Liver Physiol, 285, G20-30]. In addition, we observed, for the first time, that curcumin dramatically induced gene expression and stimulated the trans-activation activity of PPAR in activated HSC, a prerequisite for curcumin to inhibit HSC proliferation, induce apoptosis and suppress ECM production. [Zheng, S. and Chen A. (2004) Biochem. J. 384:149-157]. The underlying mechanisms remain largely to be defined.

Based on these observations, the GOALS OF MY CURRENT RESEARCH are to elucidate the molecular mechanisms of curcumin in the inhibition of HSC activation and to evaluate the potential of the phyto-chemical in the protection of the liver from fibrogenesis caused by oxidative stress. THE OVERALL HYPOTHESIS for the current research is that curcumin inhibits HSC activation and protects the liver against fibrogenesis by attenuating oxidative stress, inhibiting HSC cell growth, reducing ECM gene expression and suppressing hepatic inflammation


1987-1992 1984-1987 1978-1982
Ph. D.
Molecular Parasitology and Microbiology
University of Puerto Rico
University of Anhui, China B. S. Microbiology
University of Anhui, China

Postdoctoral Training
1995-1998 1992-1995

Postdoctoral fellow
Department of Medicine
University of Chicago Postdoctoral Fellow
Department of Oral Biology
University of Florida

Current Address

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