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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Morphological and Molecular Pathology of CCl4-Induced Hepatic Fibrosis in Connexin43-Deficient Mice

Texto completo
Autor(es):
Cogliati, Bruno [1] ; Da Silva, Tereza Cristina [1] ; Arrais Aloia, Thiago Pinheiro [2] ; Chaible, Lucas Martins [1] ; Real-Lima, Mirela Aline [1] ; Sanches, Daniel Soares [1] ; Matsuzaki, Patricia [1] ; Hernandez-Blazquez, Francisco Javier [2] ; Zaidan Dagli, Maria Lucia [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Pathol, Sch Vet Med & Anim Sci, BR-05508900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Surg, Sch Vet Med & Anim Sci, BR-05508900 Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: MICROSCOPY RESEARCH AND TECHNIQUE; v. 74, n. 5, p. 421-429, MAY 2011.
Citações Web of Science: 19
Resumo

Gap junction channels, formed by connexins (Cx), are involved in the maintenance of tissue homeostasis, cell growth, differentiation, and development. Several studies have shown that Cx43 is involved in the control of wound healing in dermal tissue. However, it remains unknown whether Cx43 plays a role in the control of liver fibrogenesis. Our study investigated the roles of Cx43 heterologous deletion on carbon tetrachloride (CCl(4))-induced hepatic fibrosis in mice. We administered CCl(4) to both Cx43-deficient (Cx43(+/-)) and wild-type mice and examined hepatocellular injury and collagen deposition by histological and ultrastructural analyses. Serum biochemical analysis was performed to quantify liver injury. Hepatocyte proliferation was analyzed immunohistochemically. Protein and messenger RNA (mRNA) expression of liver connexins were evaluated using immunohistochemistry as well as immunoblotting analysis and quantitative real-time PCR. We demonstrated that Cx43(+/-) mice developed excessive liver fibrosis compared with wild-type mice after CCl(4)-induced chronic hepatic injury, with thick and irregular collagen fibers. Histopathological evaluation showed that Cx43(+/-) mice present less necroinflammatory lesions in liver parenchyma and consequent reduction of serum aminotransferase activity. Hepatocyte cell proliferation was reduced in Cx43(+/-) mice. There was no difference in Cx32 and Cx26 protein or mRNA expression in fibrotic mice. Protein expression of Cx43 increased in CCl(4)-treated mice, although with aberrant protein location on cytoplasm of perisinusoidal cells. Our results demonstrate that Cx43 plays an important role in the control and regulation of hepatic fibrogenesis. Microsc. Res. Tech. 74:421-429, 2011. (C) 2010 Wiley-Liss, Inc. (AU)

Processo FAPESP: 05/59583-9 - Participação das conexinas 43 e 32 no desenvolvimento da fibrose hepática: estudo em camundongos geneticamente modificados
Beneficiário:Bruno Cogliati
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 06/56138-7 - Avaliação da importância das conexinas 32 e 43 na cirrose hepática induzida pela tioacetamida em camundongos
Beneficiário:Maria Lucia Zaidan Dagli
Linha de fomento: Auxílio à Pesquisa - Regular