RESUMO
Liver regeneration after partial hepatectomy is a process with various types of cells involved. The role of Kupffer cells (KCs) in liver regeneration is still controversial. In this study we isolated KCs from regenerating liver and conducted cell-specific microarray analysis. The results demonstrated that the controversial role of KCs in liver regeneration could be explained with the expression patterns of TGF-α, IL-6, TNF, and possibly IL-18 during liver regeneration. IL-18 may play an important role in negative regulation of liver regeneration. The functional profiles of gene expression in KCs also indicated that KC signaling might play a negative role in cell proliferation: signaling genes were down regulated before cell division. Immune response genes in KCs were also down regulated during liver regeneration, demonstrating similar expression profiles to that of hepatocytes. The expression patterns of key genes in these functional categories were consistent with the temporal functional profiles.
Assuntos
Células de Kupffer/metabolismo , Células de Kupffer/fisiologia , Regeneração Hepática/fisiologia , Análise em Microsséries/métodos , Animais , Divisão Celular/genética , Proliferação de Células , Células Cultivadas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hepatectomia/métodos , Interleucina-18/metabolismo , Interleucina-6/metabolismo , Fígado/metabolismo , Regeneração Hepática/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genética , Fator de Crescimento Transformador alfa/metabolismo , Fatores de Necrose Tumoral/metabolismoRESUMO
Rapidly proliferating tissue may require enhanced DNA repair capacity in order to avoid fixation of promutagenic DNA lesions to mutations. Partial hepatectomy (PH) triggers cell proliferation during liver regeneration (LR). However, little is known on how DNA repair genes change and how they are regulated at the transcriptional level during LR. In the present study, the Rat Genome 230 2.0 array was used to detect the expression profiles of DNA repair genes during LR, and differential expression of selected genes was confirmed by real-time RT-PCR. 69 DNA repair genes were found to be associated with LR, more than half of which distributed in a cluster characterized by a gradual increase at 24-72h and then returning to normal. The expression of base excision repair- and transcription-coupled repair-related genes was enhanced in the early and intermediate phases of LR, whereas the expression of genes related to HR, NHEJ and DNA cross-link repair, as well as DNA polymerases and related accessory factors, and editing or processing nucleases, were mainly enhanced in the intermediate phase. The expression changes of genes in DNA damage response were complicated throughout the whole LR. Our data also suggest that the expression of most DNA repair genes may be regulated by the cell cycle during LR.