The study on the morphogenesis of peroxisomes by the inhibition of the expression of transcription factors, PPARs.

过氧化物酶体出现在细胞中，作为细胞中小尺寸的细胞器，在胚胎发育过程中，通过各种称为过氧化物酶体增殖剂的化学物质的施用，以及各种外部生理刺激，它们的数量和大小都在增加。本研究以敲除小鼠为材料，探讨这些现象的发生机制。本研究旨在揭示以PPARα为代表的转录因子ppar调控过氧化物酶体形态发生的机制。对PPARα敲除小鼠进行两种分析，通过反义RNA法培养细胞抑制PPARα的表达。以前的实验结果已经在会议和期刊上发表过，而后来的实验却很难得到值得发表的结果。结果：1)过氧化物酶体在各种胚胎器官中以小的球形细胞器出现，其大小、数量和酶含量随发育而增加。2)低温驯化过程中棕色脂肪组织中细胞和过氧化物酶体的增殖受PPARs的激活调控。3) PPARα的激活可诱导肝细胞和过氧化物酶体增殖、脂肪肝和肝细胞癌。4) PPARα调控细胞周期。讨论：PPARα调节过氧化物酶体的大小和过氧化物酶体酶的数量，然而，其他因素可能调节它们的数量。据推测，过氧化物酶体的形态发生为小颗粒，体积增大，体积增大导致数量增加。这一假设并不总是适用于每一个过氧化物酶体增殖的病例。PPARα也可能通过调节细胞周期在肝癌发生中发挥重要作用。

Peroxisomes appear in the cells, as cell organnelles of small size in cells and they increase the number and the size during embryonic development, by the administration of various chemicals called peroxisome proliferators, and by various external physiological stimuli. The object of the study is to elucidate the mechanism of these phenomena employing knock out mice as materials. The present study was attempted to show the mechanism regulating the morphogenesis of peroxisomes by transcription factors called PPARs, represented by PPARα. Two kinds of analyses were accomplished on PPARα knock out mouse and cultured cells inhibited the expression of PPARs by anti-sense RNA method. The results of former experiment have been present at the meetings and publications in journals, however, the latter experiments were to difficult to get results deserve publication.RESULTS: 1) Peroxisomes appear as small spherical cell organnelles in various embryonic organs, their size, number and enzymes increase along with development. 2) The proliferation of cells and peroxisomes occur in brown adipose tissues during cold acclimation, which are regulated by the activation of PPARs. 3) The activation of PPARα induce proliferation of hepatocytes and peroxisomes, fatty liver, and hepatocellular carcinoma. 4) PPARα regulates cell cycle.DISCUSSION: PPARα regulates the size of peroxisomes and the amount of peroxisomal enzymes, however, other factors may regulate their number. The morphogenesis of peroxisomes has been postulated that they appear as small particles, increase their size and the increase of the size result in the increase of the number. This hypothesis may not always true in every case of peroxisome proliferation. PPARα may also play important role in hepatocarcinogenesis by regulating cell cycle.