Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway.
BACKGROUND:Liver fibrosis was viewed as a reversible process. The activation of hepatic stellate cells (HSCs) is a key event in the process of liver fibrosis. The induction of senescence of HSCs would accelerate the clearance of the activated HSCs. Previously, we demonstrated that soluble egg antige...
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ftdoajarticles:oai:doaj.org/article:98241413fbe84f02b134e1021c899b20 2023-05-15T15:10:05+02:00 Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway. Yinong Duan Jing Pan Jinling Chen Dandan Zhu Jianxin Wang Xiaolei Sun Liuting Chen Liting Wu 2016-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005268 https://doaj.org/article/98241413fbe84f02b134e1021c899b20 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5231384?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005268 https://doaj.org/article/98241413fbe84f02b134e1021c899b20 PLoS Neglected Tropical Diseases, Vol 10, Iss 12, p e0005268 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005268 2022-12-31T11:50:59Z BACKGROUND:Liver fibrosis was viewed as a reversible process. The activation of hepatic stellate cells (HSCs) is a key event in the process of liver fibrosis. The induction of senescence of HSCs would accelerate the clearance of the activated HSCs. Previously, we demonstrated that soluble egg antigens (SEA) of Schistosoma japonicum promoted the senescence of HSCs via STAT3/P53/P21 pathway. In this paper, our study was aimed to explore whether there are other signaling pathways in the process of SEA-induced HSCs aging and the underlying effect of SKP2/P27 signal on senescent HSCs. METHODOLOGY/PRINCIPAL FINDINGS:Human hepatic stellate cell line, LX-2 cells, were cultured and stimulated with SEA. Western blot and cellular immunofluorescence analysis were performed to determine the expression of senescence-associated protein, such as P27, SKP2 and FoxO3a. Besides, RNA interfering was applied to knockdown the expression of related protein. The senescence of HSCs was determined by senescence-associated β-gal staining. We found that SEA increased the expression of P27 protein, whereas it inhibited the expression of SKP2 and FoxO3a. Knockdown of P27 as well as overexpression of SKP2 both suppressed the SEA-induced senescence of HSCs. In addition, the nuclear translocation of FoxO3a from the nucleus to the cytoplasm was induced by SEA stimulation. CONCLUSIONS/SIGNIFICANCE:The present study demonstrates that SEA promotes HSCs senescence through the FoxO3a/SKP2/P27 pathway. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 12 e0005268 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Yinong Duan Jing Pan Jinling Chen Dandan Zhu Jianxin Wang Xiaolei Sun Liuting Chen Liting Wu Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Liver fibrosis was viewed as a reversible process. The activation of hepatic stellate cells (HSCs) is a key event in the process of liver fibrosis. The induction of senescence of HSCs would accelerate the clearance of the activated HSCs. Previously, we demonstrated that soluble egg antigens (SEA) of Schistosoma japonicum promoted the senescence of HSCs via STAT3/P53/P21 pathway. In this paper, our study was aimed to explore whether there are other signaling pathways in the process of SEA-induced HSCs aging and the underlying effect of SKP2/P27 signal on senescent HSCs. METHODOLOGY/PRINCIPAL FINDINGS:Human hepatic stellate cell line, LX-2 cells, were cultured and stimulated with SEA. Western blot and cellular immunofluorescence analysis were performed to determine the expression of senescence-associated protein, such as P27, SKP2 and FoxO3a. Besides, RNA interfering was applied to knockdown the expression of related protein. The senescence of HSCs was determined by senescence-associated β-gal staining. We found that SEA increased the expression of P27 protein, whereas it inhibited the expression of SKP2 and FoxO3a. Knockdown of P27 as well as overexpression of SKP2 both suppressed the SEA-induced senescence of HSCs. In addition, the nuclear translocation of FoxO3a from the nucleus to the cytoplasm was induced by SEA stimulation. CONCLUSIONS/SIGNIFICANCE:The present study demonstrates that SEA promotes HSCs senescence through the FoxO3a/SKP2/P27 pathway. |
format |
Article in Journal/Newspaper |
author |
Yinong Duan Jing Pan Jinling Chen Dandan Zhu Jianxin Wang Xiaolei Sun Liuting Chen Liting Wu |
author_facet |
Yinong Duan Jing Pan Jinling Chen Dandan Zhu Jianxin Wang Xiaolei Sun Liuting Chen Liting Wu |
author_sort |
Yinong Duan |
title |
Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway. |
title_short |
Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway. |
title_full |
Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway. |
title_fullStr |
Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway. |
title_full_unstemmed |
Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway. |
title_sort |
soluble egg antigens of schistosoma japonicum induce senescence of activated hepatic stellate cells by activation of the foxo3a/skp2/p27 pathway. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0005268 https://doaj.org/article/98241413fbe84f02b134e1021c899b20 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 12, p e0005268 (2016) |
op_relation |
http://europepmc.org/articles/PMC5231384?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005268 https://doaj.org/article/98241413fbe84f02b134e1021c899b20 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005268 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
10 |
container_issue |
12 |
container_start_page |
e0005268 |
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1766341152268615680 |