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Tytuł:
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Hedgehog signaling pathway regulates hexavalent chromium-induced liver fibrosis by activation of hepatic stellate cells.
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Autorzy:
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Yan J; College of Life Science, Shaoxing University, Shaoxing, Zhejiang, China.
Huang H; College of Life and Environmental Science, Hangzhou Normal University, Hangzhou, China.
Liu Z; Department of Pathology, Affliliated Hospital of Shaoxing University, Shaoxing, Zhejiang, China.
Shen J; Department of Pathology, Affliliated Hospital of Shaoxing University, Shaoxing, Zhejiang, China.
Ni J; College of Life Science, Shaoxing University, Shaoxing, Zhejiang, China.
Han J; Department of Pathology, Affliliated Hospital of Shaoxing University, Shaoxing, Zhejiang, China.
Wang R; College of Life Science, Qufu Normal University, Qufu City, Shandong, China.
Lin D; The Second Hospital of Shaoxing, Shaoxing, Zhejiang, China.
Hu B; College of Life Science, Shaoxing University, Shaoxing, Zhejiang, China. Electronic address: .
Jin L; College of Life Science, Shaoxing University, Shaoxing, Zhejiang, China. Electronic address: .
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Źródło:
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Toxicology letters [Toxicol Lett] 2020 Mar 01; Vol. 320, pp. 1-8. Date of Electronic Publication: 2019 Nov 19.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Amsterdam : Elsevier
Original Publication: Amsterdam, Elsevier/North Holland.
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MeSH Terms:
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Chromium*
Potassium Dichromate*
Signal Transduction*
Chemical and Drug Induced Liver Injury/*metabolism
Hedgehog Proteins/*metabolism
Hepatic Stellate Cells/*metabolism
Liver/*metabolism
Liver Cirrhosis, Experimental/*metabolism
Animals ; Chemical and Drug Induced Liver Injury/genetics ; Chemical and Drug Induced Liver Injury/pathology ; Disease Models, Animal ; Hedgehog Proteins/deficiency ; Hedgehog Proteins/genetics ; Hepatic Stellate Cells/pathology ; Liver/pathology ; Liver Cirrhosis, Experimental/chemically induced ; Liver Cirrhosis, Experimental/genetics ; Liver Cirrhosis, Experimental/pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout
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Contributed Indexing:
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Keywords: Cr(VI); Hedgehog pathway; Liver fibrosis; Shh+/−mice
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Substance Nomenclature:
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0 (Hedgehog Proteins)
0 (Shh protein, mouse)
0R0008Q3JB (Chromium)
18540-29-9 (chromium hexavalent ion)
T4423S18FM (Potassium Dichromate)
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Entry Date(s):
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Date Created: 20191123 Date Completed: 20200113 Latest Revision: 20200113
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Update Code:
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20240105
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DOI:
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10.1016/j.toxlet.2019.11.017
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PMID:
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31756458
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With the spread of hexavalent chromium [Cr(VI)] contamination, risk of exposure in non-occupational populations is increasing. The liver is the main target organ for Cr(VI) accumulation; however, the effect of long-term Cr(VI) exposure on liver toxicity is largely unknown. In this study, we investigated the effect of chronic Cr(VI) exposure on liver fibrosis and its possible mechanism. Mice were injected with Cr(VI) for two months, and our results showed Cr(VI) treatment caused liver toxicity characterized by liver structure disorganization, liver dysfunction, and antioxidant enzyme system inhibition. The development of liver fibrosis was also found via the emergence of collagen fibril deposition, increased expression of extracellular matrix-related genes, activation of hepatic stellate cells (HSCs) and increase the expression levels of Hedgehog (Hh) signaling pathway-related molecules. To demonstrate the role of Hh signaling in the regulation of Cr(VI)-induced liver fibrosis, genetically modified mice with heterozygous deficiency of Shh (Shh +/- ) were used. In the Shh +/- mice, Hh signaling, HSCs activation and liver fibrosis development were all ameliorated. In conclusion, we demonstrated that Cr(VI)-induced liver fibrosis development resulted from Hh pathway-mediated HSCs activation. Our findings strongly suggest that inhibition of Hh pathway may help in the development of new strategies for Cr(VI)-associated liver fibrosis.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
