RESUMEN
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.
Asunto(s)
Macrófagos del Hígado/metabolismo , Macrófagos del Hígado/fisiología , Regeneración Hepática/fisiología , Análisis por Micromatrices/métodos , Animales , División Celular/genética , Proliferación Celular , Células Cultivadas , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Hepatectomía/métodos , Interleucina-18/metabolismo , Interleucina-6/metabolismo , Hígado/metabolismo , Regeneración Hepática/genética , Ratas , Ratas Sprague-Dawley , Transducción de Señal/genética , Factor de Crecimiento Transformador alfa/metabolismo , Factores de Necrosis Tumoral/metabolismoRESUMEN
Rat liver regeneration after partial hepatectomy (PH) is a good model to study the regulation of cell proliferation. We isolated hepatocytes from regenerating liver at different time points after PH and used microarray Rat Genome 230 2.0 chip to analyze the functional profiles of all up- or down-regulated genes manually and with automatic gene ontological tools. We found that the transcript expressions of PH and sham operation group were apparently different. For PH group, in the priming phase (2-12 h), signaling, transcription, response to stimulus genes predominated in up-regulated genes; in the proliferation phase (24-72 h), cell proliferation genes predominated; in the termination phase (120-168 h), differentiation and translation genes predominated; while metabolism genes predominated in the down-regulated genes at all time points (2-168 h). These functional profiles are consistent with the cellular and molecular phenomenon observed during liver regeneration, and can be closely connected with the biological process. Moreover, the results indicated that not only the quantity of specific genes but also the number of the genes in the specific functional category was regulated during liver regeneration, which means the number of similar genes in a specific functional category matters as well as the regulation of the genes. The changes of the number of the regulated cell proliferation genes and metabolism genes during liver regeneration were similar to the expression patterns of some cell division genes and metabolism genes.
