The Implications of Connexin 43 Deficiency during the Early Stages of Chemically Induced Mouse Colon Carcinogenesis

Autor(es)

Santo, Sara Gomes Espirito ; da Silva, Tereza Cristina ; Vinken, Mathieu ; Cogliati, Bruno ; Barbisan, Luis Fernando ; Romualdo, Guilherme Ribeiro

• Tipo de documento: Artigo Científico
• Fonte: ANTIOXIDANTS; v. 11, n. 12, p. 16-pg., 2022-12-01.

Resumo

Colorectal cancer (CRC), associated with an increased intake of processed red meats, saturated fats, and simple carbohydrates accompanied by low dietary fiber, fruits, and vegetables consumption, presents a high epidemiological burden. Connexin43 (Cx43) protein, which forms gap junctions or hemichannels, has tumor suppressor or oncogenic activities in a cancer type- and stage-dependent manner. Cx43 expression varies during colon carcinogenesis, and its functional role is not fully understood. Thus, we evaluated the implications of Cx43 heterologous deletion (Cx43(+/-)) during the early stages of a chemically induced model of colon carcinogenesis. Female C57BL/6J mice (wild-type or Cx43(+/-)) were submitted to a colon carcinogenesis model induced by 1,2 dimethylhydrazine (DMH). Mice were euthanized eight hours (week 7) or 30 weeks (week 37) after the last DMH administration to evaluate subacute colon toxicity outcomes or the burden of (pre)neoplastic lesions, respectively. At week 7, Cx43 deficiency inferred no alterations in the DMH-induced increase in systemic (peripheral blood), in situ (colonocytes) DNA damage, and apoptosis in the colonocytes. At week 30, Cx43(+/-) mice presented an increase in preneoplastic aberrant crypt foci (ACF) multiplicity, while no alterations were observed in colorectal adenoma (CRA) occurrence, multiplicity, volume, proliferation, growth, and beta-catenin immunoexpression. Similarly, an in silico analysis of human CRA showed decreased mRNA expression of Cx43 with no correlation with proliferation, apoptosis, and beta-catenin markers. These findings indicate the discrete role of Cx43 in the early stages of chemically induced mouse colon carcinogenesis. (AU)

• Processo FAPESP: 18/10953-9 - As conexinas, panexinas e seus hemi(canais) são novos biomarcadores e alvos terapêuticos no prognóstico e terapia do câncer hepático?
• Beneficiário: Bruno Cogliati
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/02175-1 - Caracterização da dinâmica de renovação das células estreladas hepáticas (HSC) e sua contribuição na esteatohepatite não alcoólica (NASH)
• Beneficiário: Bruno Cogliati
• Modalidade de apoio: Bolsas no Exterior - Pesquisa