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The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARgamma in rat activated hepatic stellate cell in vitro.
Lab Invest. 2007 May; 87(5):488-98.LI

Abstract

Activation of hepatic stellate cells (HSC), the major effector in hepatic fibrogenesis, is coupled with sequential alterations in expression of genes, including the upregulation of platelet-derived growth factor-beta receptor (PDGF-betaR) and epidermal growth factor receptor (EGFR), as well as the down-regulation of the peroxisome proliferator-activated receptor-gamma (PPARgamma). However, the relationship among the alterations in expression of the genes and the activation of their signaling in activated HSC remains obscure. We recently showed that curcumin, the yellow pigment in curry, inhibited cell growth and induced gene expression of endogenous PPARgamma in activated HSC in vitro. The present study is to elucidate the underlying mechanisms, focusing on the impacts of PDGF and EGF signaling. It is hypothesized that the interruption of the PDGF and EGF signaling pathways by curcumin might stimulate gene expression of PPARgamma in activated HSC. Our results in this report indicate that the activation of PDGF or EGF signaling by exogenous PDGF or EGF inhibits PPARgamma gene expression in passaged HSC. Curcumin interrupts PDGF and EGF signaling demonstrated by inhibiting tyrosine phosphorylation of PDGF-betaR and EGFR and by reducing the levels of phosphorylated phosphatidylinositol-3 kinase (PI-3K/AKT), extracellular signal-regulated kinase (ERK) and the Jun N-terminal kinase (JNK). The blockade of PI-3K/AKT, ERK or JNK signaling negatively regulates PPARgamma gene expression in activated HSC, leading to the reduction in cell growth, including inducing cell arrest and apoptosis. Our results collectively demonstrate that the interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARgamma in activated HSC. These results provide novel insights into the mechanisms of curcumin in the induction of PPARgamma gene expression in activated HSC.

Authors+Show Affiliations

Department of Biochemistry, Nantong University, Nantong, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17372590

Citation

Zhou, Yajun, et al. "The Interruption of the PDGF and EGF Signaling Pathways By Curcumin Stimulates Gene Expression of PPARgamma in Rat Activated Hepatic Stellate Cell in Vitro." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 87, no. 5, 2007, pp. 488-98.
Zhou Y, Zheng S, Lin J, et al. The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARgamma in rat activated hepatic stellate cell in vitro. Lab Invest. 2007;87(5):488-98.
Zhou, Y., Zheng, S., Lin, J., Zhang, Q. J., & Chen, A. (2007). The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARgamma in rat activated hepatic stellate cell in vitro. Laboratory Investigation; a Journal of Technical Methods and Pathology, 87(5), 488-98.
Zhou Y, et al. The Interruption of the PDGF and EGF Signaling Pathways By Curcumin Stimulates Gene Expression of PPARgamma in Rat Activated Hepatic Stellate Cell in Vitro. Lab Invest. 2007;87(5):488-98. PubMed PMID: 17372590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARgamma in rat activated hepatic stellate cell in vitro. AU - Zhou,Yajun, AU - Zheng,Shizhong, AU - Lin,Jianguo, AU - Zhang,Qian-Jin, AU - Chen,Anping, Y1 - 2007/03/19/ PY - 2007/3/21/pubmed PY - 2007/6/15/medline PY - 2007/3/21/entrez SP - 488 EP - 98 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab Invest VL - 87 IS - 5 N2 - Activation of hepatic stellate cells (HSC), the major effector in hepatic fibrogenesis, is coupled with sequential alterations in expression of genes, including the upregulation of platelet-derived growth factor-beta receptor (PDGF-betaR) and epidermal growth factor receptor (EGFR), as well as the down-regulation of the peroxisome proliferator-activated receptor-gamma (PPARgamma). However, the relationship among the alterations in expression of the genes and the activation of their signaling in activated HSC remains obscure. We recently showed that curcumin, the yellow pigment in curry, inhibited cell growth and induced gene expression of endogenous PPARgamma in activated HSC in vitro. The present study is to elucidate the underlying mechanisms, focusing on the impacts of PDGF and EGF signaling. It is hypothesized that the interruption of the PDGF and EGF signaling pathways by curcumin might stimulate gene expression of PPARgamma in activated HSC. Our results in this report indicate that the activation of PDGF or EGF signaling by exogenous PDGF or EGF inhibits PPARgamma gene expression in passaged HSC. Curcumin interrupts PDGF and EGF signaling demonstrated by inhibiting tyrosine phosphorylation of PDGF-betaR and EGFR and by reducing the levels of phosphorylated phosphatidylinositol-3 kinase (PI-3K/AKT), extracellular signal-regulated kinase (ERK) and the Jun N-terminal kinase (JNK). The blockade of PI-3K/AKT, ERK or JNK signaling negatively regulates PPARgamma gene expression in activated HSC, leading to the reduction in cell growth, including inducing cell arrest and apoptosis. Our results collectively demonstrate that the interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARgamma in activated HSC. These results provide novel insights into the mechanisms of curcumin in the induction of PPARgamma gene expression in activated HSC. SN - 0023-6837 UR - https://www.unboundmedicine.com/medline/citation/17372590/The_interruption_of_the_PDGF_and_EGF_signaling_pathways_by_curcumin_stimulates_gene_expression_of_PPARgamma_in_rat_activated_hepatic_stellate_cell_in_vitro_ L2 - https://doi.org/10.1038/labinvest.3700532 DB - PRIME DP - Unbound Medicine ER -