Interleukin-6 mediates angiotensinogen gene expression during liver regeneration.

<h4>Background</h4>Angiotensinogen is the precursor of angiotensin II, which is associated with ischemia-reperfusion injury. Angiotensin II reduces liver regeneration after hepatectomy and causes dysfunction and failure of reduced-size liver transplants. However, the regulation of angiot...

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Autores principales:	Hong-Shiee Lai, Wen-Hsi Lin, Shuo-Lun Lai, Hao-Yu Lin, Wen-Ming Hsu, Chia-Hung Chou, Po-Huang Lee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/97de5b49089e4ed6a968817585e373ba
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spelling	oai:doaj.org-article:97de5b49089e4ed6a968817585e373ba2021-11-18T07:38:48ZInterleukin-6 mediates angiotensinogen gene expression during liver regeneration.1932-620310.1371/journal.pone.0067868https://doaj.org/article/97de5b49089e4ed6a968817585e373ba2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23844114/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Angiotensinogen is the precursor of angiotensin II, which is associated with ischemia-reperfusion injury. Angiotensin II reduces liver regeneration after hepatectomy and causes dysfunction and failure of reduced-size liver transplants. However, the regulation of angiotensinogen during liver regeneration is still unclear.<h4>Aims</h4>To investigate the regulation of angiotensinogen during liver regeneration for preventing angiotensin II-related ischemia-reperfusion injury during liver regeneration.<h4>Methods</h4>A mouse in vitro partial hepatectomy animal model was used to evaluate the expression of interleukin-6 (IL-6) and angiotensinogen during liver regeneration. Serum IL-6 and angiotensinogen were detected by enzyme immunoassay (EIA). Angiotensinogen mRNA was detected by RT-PCR. Tissue levels of angiotensinogen protein were detected by Western blot analysis. Primary cultures of mouse hepatocytes were used to investigate IL-6-induced angiotensinogen. Chemical inhibitors were used to perturb signal transduction pathways. Synthetic double-stranded oligodeoxynucleotides (ODNs) were used as 'decoy' cis-elements to investigate transcription. Ki 67 staining and quantification were used to verify liver regeneration.<h4>Results</h4>In the in vivo model, the levels of serum IL-6 and angiotensinogen correlated. In the in vitro model, IL-6 transcriptionally regulated angiotensinogen expression. Additionally, IL-6 mediated angiotensinogen expression through the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) and JAK/p38 signaling. Decoy ODN analyses revealed that STAT3 and nuclear factor-kB (NF-kB) also played critical roles in the transcriptional regulation of angiotensinogen by IL-6. IL-6-mediated signaling, JAK2, STAT3 and p38 inhibitors reduced angiotensinogen expression in the partially hepatectomized mice.<h4>Conclusion</h4>During liver regeneration, IL-6-enhanced angiotensinogen expression is dependent on the JAK/STAT3 and JAK/p38/NF-kB signaling pathways. Interruption of the molecular mechanisms of angiotensinogen regulation may be applied as the basis of therapeutic strategies for preventing angiotensin II-related ischemia-reperfusion injury during liver regeneration.Hong-Shiee LaiWen-Hsi LinShuo-Lun LaiHao-Yu LinWen-Ming HsuChia-Hung ChouPo-Huang LeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e67868 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hong-Shiee Lai Wen-Hsi Lin Shuo-Lun Lai Hao-Yu Lin Wen-Ming Hsu Chia-Hung Chou Po-Huang Lee Interleukin-6 mediates angiotensinogen gene expression during liver regeneration.
description	<h4>Background</h4>Angiotensinogen is the precursor of angiotensin II, which is associated with ischemia-reperfusion injury. Angiotensin II reduces liver regeneration after hepatectomy and causes dysfunction and failure of reduced-size liver transplants. However, the regulation of angiotensinogen during liver regeneration is still unclear.<h4>Aims</h4>To investigate the regulation of angiotensinogen during liver regeneration for preventing angiotensin II-related ischemia-reperfusion injury during liver regeneration.<h4>Methods</h4>A mouse in vitro partial hepatectomy animal model was used to evaluate the expression of interleukin-6 (IL-6) and angiotensinogen during liver regeneration. Serum IL-6 and angiotensinogen were detected by enzyme immunoassay (EIA). Angiotensinogen mRNA was detected by RT-PCR. Tissue levels of angiotensinogen protein were detected by Western blot analysis. Primary cultures of mouse hepatocytes were used to investigate IL-6-induced angiotensinogen. Chemical inhibitors were used to perturb signal transduction pathways. Synthetic double-stranded oligodeoxynucleotides (ODNs) were used as 'decoy' cis-elements to investigate transcription. Ki 67 staining and quantification were used to verify liver regeneration.<h4>Results</h4>In the in vivo model, the levels of serum IL-6 and angiotensinogen correlated. In the in vitro model, IL-6 transcriptionally regulated angiotensinogen expression. Additionally, IL-6 mediated angiotensinogen expression through the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) and JAK/p38 signaling. Decoy ODN analyses revealed that STAT3 and nuclear factor-kB (NF-kB) also played critical roles in the transcriptional regulation of angiotensinogen by IL-6. IL-6-mediated signaling, JAK2, STAT3 and p38 inhibitors reduced angiotensinogen expression in the partially hepatectomized mice.<h4>Conclusion</h4>During liver regeneration, IL-6-enhanced angiotensinogen expression is dependent on the JAK/STAT3 and JAK/p38/NF-kB signaling pathways. Interruption of the molecular mechanisms of angiotensinogen regulation may be applied as the basis of therapeutic strategies for preventing angiotensin II-related ischemia-reperfusion injury during liver regeneration.
format	article
author	Hong-Shiee Lai Wen-Hsi Lin Shuo-Lun Lai Hao-Yu Lin Wen-Ming Hsu Chia-Hung Chou Po-Huang Lee
author_facet	Hong-Shiee Lai Wen-Hsi Lin Shuo-Lun Lai Hao-Yu Lin Wen-Ming Hsu Chia-Hung Chou Po-Huang Lee
author_sort	Hong-Shiee Lai
title	Interleukin-6 mediates angiotensinogen gene expression during liver regeneration.
title_short	Interleukin-6 mediates angiotensinogen gene expression during liver regeneration.
title_full	Interleukin-6 mediates angiotensinogen gene expression during liver regeneration.
title_fullStr	Interleukin-6 mediates angiotensinogen gene expression during liver regeneration.
title_full_unstemmed	Interleukin-6 mediates angiotensinogen gene expression during liver regeneration.
title_sort	interleukin-6 mediates angiotensinogen gene expression during liver regeneration.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/97de5b49089e4ed6a968817585e373ba
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_version_	1718423176502837248

Interleukin-6 mediates angiotensinogen gene expression during liver regeneration.

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