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1.
Vet J ; 184(3): 308-14, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19369099

RESUMO

The liver progenitor cell compartment in the normal canine liver and in spontaneous canine acute (AH) and chronic hepatitis (CH) was morphologically characterised and compared to its human equivalents. Immunohistochemistry was performed for cytokeratin-7 (CK7), human hepatocyte marker (Hep Par 1), multidrug resistance-associated protein-2 (MRP2), and breast cancer resistance protein (BCRP) on paraffin and frozen sections from canine and human tissues. Normal liver showed similar morphology and immunohistochemical reaction of the progenitor cell compartment/canal of Hering in man and dog. In addition, a ductular reaction, comparable in terms of severity, location and immunohistochemical characteristics, was observed in canine and human AH and CH. CK7 was a good marker for canine progenitor cells, including intermediate cells, which were positively identified in cases of AH and CH. In both species, BCRP was expressed in both hepatocytes and bile ducts of the normal liver, and in ductular reaction in AH and CH. MRP2 detected bile canalicular membranes in man and dog. These findings underline the similarities between canine and human liver reaction patterns and may offer mutual advantage for comparative research in human and canine spontaneous liver diseases.


Assuntos
Hepatite Animal/metabolismo , Hepatite/metabolismo , Hepatócitos/citologia , Imuno-Histoquímica , Fígado/citologia , Células-Tronco/citologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/análise , Animais , Cães , Hepatite/patologia , Hepatite Animal/patologia , Hepatócitos/metabolismo , Humanos , Imuno-Histoquímica/veterinária , Queratina-7/análise , Fígado/patologia , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/análise , Proteínas de Neoplasias/análise , Especificidade da Espécie , Células-Tronco/metabolismo
2.
Gut ; 52(7): 1060-7, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12801967

RESUMO

BACKGROUND AND AIM: Liver regeneration after severe liver damage depends in part on proliferation and differentiation of hepatic progenitor cells (HPCs). Under these conditions they must be able to withstand the toxic milieu of the damaged liver. ATP binding cassette (ABC) transporters are cytoprotective efflux pumps that may contribute to the preservation of these cells. The aim of this study was to determine the ABC transporter phenotype of HPCs. METHODS: HPC activation was studied in rats treated with 2- acetylaminofluorene (2-AAF) followed by partial hepatectomy (PHx). ABC transporter gene expression was determined by real time detection reverse transcription-polymerase chain reaction in isolated HPCs, hepatocytes, cholangiocytes, and cultured progenitor cell-like RLF phi 13 cells and by immunohistochemistry of total liver samples. ABC transporter efflux activity was studied in RLF phi 13 cells by flow cytometry. RESULTS: 2-AAF/PHx treated animals showed increased hepatic mRNA levels of the genes encoding multidrug resistance proteins Mdr1b, Mrp1, and Mrp3. Immunohistochemistry demonstrated expression of Mrp1 and Mrp3 proteins in periportal progenitor cells and of the Mdr1b protein in periportal hepatocytes. Freshly isolated Thy-1 positive cells and cultured RLF phi 13 progenitor cells highly expressed Mrp1 and Mrp3 mRNA while the hepatocyte specific transporters Mdr2, Bsep, Mrp2, and Mrp6 were only minimally expressed. Blocking Mrp activity by MK-571 resulted in accumulation of the Mrp specific substrate carboxyfluorescein in RLF phi 13 cells. CONCLUSION: HPCs express high levels of active Mrp1 and Mrp3. These may have a cytoprotective role in conditions of severe hepatotoxicity.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Fígado/citologia , Células-Tronco/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/análise , Transportadores de Cassetes de Ligação de ATP/análise , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Divisão Celular/fisiologia , Linhagem Celular , Citometria de Fluxo/métodos , Expressão Gênica , Genes MDR/genética , Imuno-Histoquímica/métodos , Masculino , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos F344 , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Organismos Livres de Patógenos Específicos
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