MAPK Signaling Pathway Regulates p27 Phosphorylation at Threonin 187 as Part of the Mechanism Triggered by Early-Weaning to Induce Cell Proliferation in Rat Gastric Mucosa

Autor(es)

Osaki, Luciana H. ^[1] ; Gama, Patricia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 6 JUN 7 2013.
• Citações Web of Science: 8

Resumo

During rat postnatal development, gastric cell proliferation and differentiation depend on many elements, which include dietary pattern, hormones, growth factors and their signaling pathways. Among them, EGFR activity is increased through MAPK and Src cascades in response to early weaning that represents the abrupt transition from milk to solid food. We herein investigated the direct involvement of ERK pathway in the control of cell cycle progression during early weaning, and studied the specific role of p27. At 15 days, Wistar rats were separated from dams, fed with powdered chow and daily injected with PD98059 (MEK inhibitor, 300 mu g/kg) or 0.5% DMSO (control). By using HE staining and immunohistochemistry for PCNA, we respectively detected mitotic (MI) and proliferative (PI) indices in 18-day-old pups, and observed that both were reduced by PD98059. As cell cycle-related proteins (cyclin E, CDK2, cyclin D1, CDK4, p21 and p27) are involved in proliferative regulation, we compared samples obtained at 17 days in the morning (17 d) and evening (17.5 d). We found that they were not altered after ERK inhibition, but cyclin D1, p21 and p27 levels changed throughout the day in the control group. As p27 activity depends on its integrity, we studied p27 phosphorylation (threonin 187), and observed that ERK inhibition reduced this process. We suggest that MAPK pathway interferes in the regulation of p27 function in the gastric mucosa during early weaning, possibly by controlling its degradation, and altogether this mechanism might contribute to the increase of epithelial proliferation at this condition. (AU)

• Processo FAPESP: 11/07089-1 - Avaliação da interação entre vias de sinalização no controle da proliferação e diferenciação celular na mucosa gástrica
• Beneficiário: Patrícia Gama
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/17851-5 - Papel de vias de sinalização no controle da proliferação e diferenciação celular na mucosa gástrica
• Beneficiário: Luciana Harumi Osaki
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado