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Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro
Diabetes is featured by hyperglycemia, which facilitates the formation of advanced glycation end-products (AGEs). AGEs are a causal factor in development of diabetic complications. AGE receptor-1 (AGE-R1) is responsible for detoxification and clearance of AGEs. Type 2 diabetes mellitus is commonly a...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365656/ https://www.ncbi.nlm.nih.gov/pubmed/22449800 http://dx.doi.org/10.1038/labinvest.2012.53 |
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author | Lin, Jianguo Tang, Youcai Kang, Qiaohua Chen, Anping |
author_facet | Lin, Jianguo Tang, Youcai Kang, Qiaohua Chen, Anping |
author_sort | Lin, Jianguo |
collection | PubMed |
description | Diabetes is featured by hyperglycemia, which facilitates the formation of advanced glycation end-products (AGEs). AGEs are a causal factor in development of diabetic complications. AGE receptor-1 (AGE-R1) is responsible for detoxification and clearance of AGEs. Type 2 diabetes mellitus is commonly accompanied by non-alcoholic steatohepatitis, which could cause hepatic fibrosis. Little attention has been paid to effects of AGEs on hepatic fibrogenesis. Curcumin, a phytochemical from turmeric, has been reported to inhibit the activation of hepatic stellate cells (HSCs), the major effectors during hepatic fibrogenesis, and to protect against hepatic fibrogenesis in vitro and in vivo. The current study was designed to evaluate effects of AGEs on inducing HSC activation, to assess the role of curcumin in diminishing the AGE effects and to explore the underlying mechanisms. Our results showed that AGEs stimulated HSC activation by inducing cell proliferation and expression of genes relevant to HSC activation, which were abrogated by curcumin. Curcumin induced gene expression of AGE-R1 in passaged HSCs, which might facilitate the attenuation of the stimulatory effects of AGEs on the activation of HSCs. Further experiments revealed that curcumin inhibited the activity of extracellular signal-regulated kinase (ERK) and induced gene expression and the activity of peroxisome proliferator-activated receptor-gamma (PPARγ), leading to the induction of AGE-R1 gene expression. In summary, AGEs stimulated HSC activation. Curcumin eliminated the AGE effects at least partially by inducing AGE-R1 gene expression. The process was mediated by inhibiting ERK activity, inducing gene expression of PPARγ and stimulating its trans-activity. |
format | Online Article Text |
id | pubmed-3365656 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-33656562012-12-01 Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro Lin, Jianguo Tang, Youcai Kang, Qiaohua Chen, Anping Lab Invest Article Diabetes is featured by hyperglycemia, which facilitates the formation of advanced glycation end-products (AGEs). AGEs are a causal factor in development of diabetic complications. AGE receptor-1 (AGE-R1) is responsible for detoxification and clearance of AGEs. Type 2 diabetes mellitus is commonly accompanied by non-alcoholic steatohepatitis, which could cause hepatic fibrosis. Little attention has been paid to effects of AGEs on hepatic fibrogenesis. Curcumin, a phytochemical from turmeric, has been reported to inhibit the activation of hepatic stellate cells (HSCs), the major effectors during hepatic fibrogenesis, and to protect against hepatic fibrogenesis in vitro and in vivo. The current study was designed to evaluate effects of AGEs on inducing HSC activation, to assess the role of curcumin in diminishing the AGE effects and to explore the underlying mechanisms. Our results showed that AGEs stimulated HSC activation by inducing cell proliferation and expression of genes relevant to HSC activation, which were abrogated by curcumin. Curcumin induced gene expression of AGE-R1 in passaged HSCs, which might facilitate the attenuation of the stimulatory effects of AGEs on the activation of HSCs. Further experiments revealed that curcumin inhibited the activity of extracellular signal-regulated kinase (ERK) and induced gene expression and the activity of peroxisome proliferator-activated receptor-gamma (PPARγ), leading to the induction of AGE-R1 gene expression. In summary, AGEs stimulated HSC activation. Curcumin eliminated the AGE effects at least partially by inducing AGE-R1 gene expression. The process was mediated by inhibiting ERK activity, inducing gene expression of PPARγ and stimulating its trans-activity. 2012-03-26 2012-06 /pmc/articles/PMC3365656/ /pubmed/22449800 http://dx.doi.org/10.1038/labinvest.2012.53 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Lin, Jianguo Tang, Youcai Kang, Qiaohua Chen, Anping Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro |
title | Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro |
title_full | Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro |
title_fullStr | Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro |
title_full_unstemmed | Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro |
title_short | Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro |
title_sort | curcumin eliminates the inhibitory effect of advanced glycation end-products (ages) on gene expression of age receptor-1 in hepatic stellate cells in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365656/ https://www.ncbi.nlm.nih.gov/pubmed/22449800 http://dx.doi.org/10.1038/labinvest.2012.53 |
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