An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features

Detalhes bibliográficos
Autor(a) principal: Romualdo, Guilherme Ribeiro [UNESP]
Data de Publicação: 2017
Outros Autores: Grassi, Tony Fernando [UNESP], Goto, Renata Leme [UNESP], Tablas, Mariana Baptista [UNESP], Bidinotto, Lucas Tadeu, Fernandes, Ana Angélica Henrique [UNESP], Cogliati, Bruno, Barbisan, Luís Fernando [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.toxlet.2017.09.015
http://hdl.handle.net/11449/175252
Resumo: This study aimed the integrative characterization of morphological, biochemical and molecular features of chemically-induced cirrhosis-associated hepatocarcinogenesis. Thus, male Wistar rats were submitted to a diethylnitrosamine (DEN)/thioacetamide (TAA)-induced model. Liver tissue was processed for global gene expression, histopathological and collagen evaluations; as well as immunohistochemical and oxidative stress analysis. Gene Ontology and functional analysis showed the upregulation of extracellular matrix deposition genes, such as collagen type I alpha 1 and 2 (Col1α1 and Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 genes (Timp1 and Timp2). In agreement these findings, animals presented extensive liver cirrhosis with increased collagen deposition (Sirius red). Besides, the animals developed many glutathione S-transferase pi (GST-P)-positive preneoplastic lesions showing high cell proliferation (Ki-67), in keeping with the Gstp1 and Gstp2 increased gene expression. DEN/TAA-treated rats also showed the upregulation of tumorigenesis-related annexin A2 gene (Anxa2) and few neoplastic lesions (hepatocellular adenomas, carcinomas, and cholangiocarcinoma). In contrast, gene expression and activity of antioxidant enzymes were decreased (glutathione peroxidase, total glutathione-S-transferase, and catalase). The model featured remarkable similarities to human hepatocarcinogenesis. Our findings could bring up new molecular insights into cirrhosis-associated hepatocarcinogenesis, and provide a suitable animal model for the establishment of further diagnostic, preventive and therapeutic approaches.
id UNSP_484a74e3ec603ddb636db5552d327754
oai_identifier_str oai:repositorio.unesp.br:11449/175252
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular featuresDiethylnitrosamineHepatocarcinogenesisLiver cirrhosisOligo microarrayThioacetamideWistar ratsThis study aimed the integrative characterization of morphological, biochemical and molecular features of chemically-induced cirrhosis-associated hepatocarcinogenesis. Thus, male Wistar rats were submitted to a diethylnitrosamine (DEN)/thioacetamide (TAA)-induced model. Liver tissue was processed for global gene expression, histopathological and collagen evaluations; as well as immunohistochemical and oxidative stress analysis. Gene Ontology and functional analysis showed the upregulation of extracellular matrix deposition genes, such as collagen type I alpha 1 and 2 (Col1α1 and Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 genes (Timp1 and Timp2). In agreement these findings, animals presented extensive liver cirrhosis with increased collagen deposition (Sirius red). Besides, the animals developed many glutathione S-transferase pi (GST-P)-positive preneoplastic lesions showing high cell proliferation (Ki-67), in keeping with the Gstp1 and Gstp2 increased gene expression. DEN/TAA-treated rats also showed the upregulation of tumorigenesis-related annexin A2 gene (Anxa2) and few neoplastic lesions (hepatocellular adenomas, carcinomas, and cholangiocarcinoma). In contrast, gene expression and activity of antioxidant enzymes were decreased (glutathione peroxidase, total glutathione-S-transferase, and catalase). The model featured remarkable similarities to human hepatocarcinogenesis. Our findings could bring up new molecular insights into cirrhosis-associated hepatocarcinogenesis, and provide a suitable animal model for the establishment of further diagnostic, preventive and therapeutic approaches.Department of Pathology Botucatu Medical School São Paulo State University (UNESP)Department of Morphology Institute of Biosciences São Paulo State University (UNESP)Molecular Oncology Research Center Barretos Cancer HospitalBarretos School of Health Sciences, Dr. Paulo Prata − FACISBDepartment of Chemistry and Biochemistry Institute of Biosciences São Paulo State University (UNESP)Department of Pathology School of Veterinary Medicine and Animal Science São Paulo University (USP)Department of Pathology Botucatu Medical School São Paulo State University (UNESP)Department of Morphology Institute of Biosciences São Paulo State University (UNESP)Department of Chemistry and Biochemistry Institute of Biosciences São Paulo State University (UNESP)Universidade Estadual Paulista (Unesp)Barretos Cancer HospitalBarretos School of Health SciencesUniversidade de São Paulo (USP)Romualdo, Guilherme Ribeiro [UNESP]Grassi, Tony Fernando [UNESP]Goto, Renata Leme [UNESP]Tablas, Mariana Baptista [UNESP]Bidinotto, Lucas TadeuFernandes, Ana Angélica Henrique [UNESP]Cogliati, BrunoBarbisan, Luís Fernando [UNESP]2018-12-11T17:15:00Z2018-12-11T17:15:00Z2017-11-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article84-94application/pdfhttp://dx.doi.org/10.1016/j.toxlet.2017.09.015Toxicology Letters, v. 281, p. 84-94.1879-31690378-4274http://hdl.handle.net/11449/17525210.1016/j.toxlet.2017.09.0152-s2.0-850298464772-s2.0-85029846477.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengToxicology Letters1,103info:eu-repo/semantics/openAccess2024-09-03T13:14:42Zoai:repositorio.unesp.br:11449/175252Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:14:42Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features
title An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features
spellingShingle An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features
Romualdo, Guilherme Ribeiro [UNESP]
Diethylnitrosamine
Hepatocarcinogenesis
Liver cirrhosis
Oligo microarray
Thioacetamide
Wistar rats
title_short An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features
title_full An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features
title_fullStr An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features
title_full_unstemmed An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features
title_sort An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features
author Romualdo, Guilherme Ribeiro [UNESP]
author_facet Romualdo, Guilherme Ribeiro [UNESP]
Grassi, Tony Fernando [UNESP]
Goto, Renata Leme [UNESP]
Tablas, Mariana Baptista [UNESP]
Bidinotto, Lucas Tadeu
Fernandes, Ana Angélica Henrique [UNESP]
Cogliati, Bruno
Barbisan, Luís Fernando [UNESP]
author_role author
author2 Grassi, Tony Fernando [UNESP]
Goto, Renata Leme [UNESP]
Tablas, Mariana Baptista [UNESP]
Bidinotto, Lucas Tadeu
Fernandes, Ana Angélica Henrique [UNESP]
Cogliati, Bruno
Barbisan, Luís Fernando [UNESP]
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Barretos Cancer Hospital
Barretos School of Health Sciences
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Romualdo, Guilherme Ribeiro [UNESP]
Grassi, Tony Fernando [UNESP]
Goto, Renata Leme [UNESP]
Tablas, Mariana Baptista [UNESP]
Bidinotto, Lucas Tadeu
Fernandes, Ana Angélica Henrique [UNESP]
Cogliati, Bruno
Barbisan, Luís Fernando [UNESP]
dc.subject.por.fl_str_mv Diethylnitrosamine
Hepatocarcinogenesis
Liver cirrhosis
Oligo microarray
Thioacetamide
Wistar rats
topic Diethylnitrosamine
Hepatocarcinogenesis
Liver cirrhosis
Oligo microarray
Thioacetamide
Wistar rats
description This study aimed the integrative characterization of morphological, biochemical and molecular features of chemically-induced cirrhosis-associated hepatocarcinogenesis. Thus, male Wistar rats were submitted to a diethylnitrosamine (DEN)/thioacetamide (TAA)-induced model. Liver tissue was processed for global gene expression, histopathological and collagen evaluations; as well as immunohistochemical and oxidative stress analysis. Gene Ontology and functional analysis showed the upregulation of extracellular matrix deposition genes, such as collagen type I alpha 1 and 2 (Col1α1 and Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 genes (Timp1 and Timp2). In agreement these findings, animals presented extensive liver cirrhosis with increased collagen deposition (Sirius red). Besides, the animals developed many glutathione S-transferase pi (GST-P)-positive preneoplastic lesions showing high cell proliferation (Ki-67), in keeping with the Gstp1 and Gstp2 increased gene expression. DEN/TAA-treated rats also showed the upregulation of tumorigenesis-related annexin A2 gene (Anxa2) and few neoplastic lesions (hepatocellular adenomas, carcinomas, and cholangiocarcinoma). In contrast, gene expression and activity of antioxidant enzymes were decreased (glutathione peroxidase, total glutathione-S-transferase, and catalase). The model featured remarkable similarities to human hepatocarcinogenesis. Our findings could bring up new molecular insights into cirrhosis-associated hepatocarcinogenesis, and provide a suitable animal model for the establishment of further diagnostic, preventive and therapeutic approaches.
publishDate 2017
dc.date.none.fl_str_mv 2017-11-05
2018-12-11T17:15:00Z
2018-12-11T17:15:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.toxlet.2017.09.015
Toxicology Letters, v. 281, p. 84-94.
1879-3169
0378-4274
http://hdl.handle.net/11449/175252
10.1016/j.toxlet.2017.09.015
2-s2.0-85029846477
2-s2.0-85029846477.pdf
url http://dx.doi.org/10.1016/j.toxlet.2017.09.015
http://hdl.handle.net/11449/175252
identifier_str_mv Toxicology Letters, v. 281, p. 84-94.
1879-3169
0378-4274
10.1016/j.toxlet.2017.09.015
2-s2.0-85029846477
2-s2.0-85029846477.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxicology Letters
1,103
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 84-94
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
_version_ 1810021372041101312