Cell cross-talk mediates PPARalpha null hepatocyte proliferation after peroxisome proliferator exposure.
Cell cross-talk mediates PPARalpha null hepatocyte proliferation after peroxisome proliferator exposure.
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过氧化物酶体增殖物暴露后，细胞串扰介导 PPARα 无效肝细胞增殖。
DOI：
10.1093/carcin/bgg180
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Sandgren,EricP
中科院分区：
文献类型：
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作者：
Weglarz,TeresaC;Sandgren,EricP
过氧化物酶体增殖物激活受体α(PPARα)介导肝脏对过氧化物酶体增殖物化合物的反应。这些反应包括诱导特定的肝酶、过氧化物酶和肝细胞的增殖。PPARα缺失小鼠在体内所有细胞中都缺乏受体，对过氧化物酶体增殖物不产生反应，这表明肝细胞增殖和其他反应至少需要在某些细胞中存在这种受体。为了确定每种反应是否需要PPARα在肝细胞中特异性地存在，我们使用肝细胞移植在PPARα阴性或阳性宿主中产生由PPARα阴性和阳性肝细胞组成的嵌合肝。当暴露于过氧化物酶体增殖剂时，过氧化物体的增殖和酶诱导仅限于受体阳性的肝细胞，表明这些反应是细胞自主的，与肝细胞受体状态有关。然而，无论宿主受体状态如何，嵌合肝脏中PPARα缺失和阳性的肝细胞都表现出高的DNA合成，只要至少有一些肝细胞含有受体。这些发现表明，对过氧化物酶体增殖物的促有丝分裂反应并不需要所有肝细胞中的PPARα。
Peroxisome proliferator activated receptorα (PPARα) mediates the liver's responses to peroxisome proliferator compounds. These responses include induction of specific hepatic enzymes, peroxisome proliferation and hepatocyte proliferation. PPARα null mice, which lack receptor in all cells of the body, do not respond to peroxisome proliferators, indicating that hepatocellular proliferation and other responses require the presence of this receptor in at least some cells. To determine if PPARα is required specifically in hepatocytes for each response, we used hepatocyte transplantation to generate chimeric livers composed of PPARα null and positive hepatocytes in PPARα null or positive hosts. Upon exposure to a peroxisome proliferator, peroxisome proliferation and enzyme induction were restricted to receptor positive hepatocytes, indicating that these responses are cell autonomous with respect to hepatocyte receptor status. However, both PPARα null and positive hepatocytes in chimeric livers displayed elevated DNA synthesis regardless of host receptor status, as long as at least some hepatocytes contained receptor. These findings indicate that the mitogenic response to peroxisome proliferators does not require PPARα in all hepatocytes.