HGF-, EGF-, and dexamethasone-induced gene expression patterns during formation of tissue in hepatic organoid cultures.
HGF-, EGF-, and dexamethasone-induced gene expression patterns during formation of tissue in hepatic organoid cultures.
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DOI：
10.3727/000000003108748964
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Michalopoulos GK;Bowen WC;Mulè K;Luo J
皮质类固醇、HGF和EGF在肝脏生物学中起重要作用。我们以前已经表明，这些分子是在复杂的类器官培养中形成具有特定组织学的组织所必需的。地塞米松抑制生长并诱导肝细胞成熟; HGF和EGF是形成非上皮成分所必需的。所有这三种都是胆管上皮形成所必需的。皮质类固醇、HGF和EGF介导其在肝组织形成中的作用的基因表达模式是不同的。这些模式影响许多基因家族，并详细描述。在主要发现方面，地塞米松诱导HNF 4和C/EBP-α的表达，这是肝细胞分化的必需转录因子。它通过抑制许多与肝脏和其他组织中的生长相关的分子来抑制肝细胞生长，包括IL 6、CXC-趋化因子受体、双调蛋白、考克斯-2、HIF等。HGF和EGF诱导TGF-β家族的所有成员。它们还诱导多个CNS相关基因，可能与星状细胞相关。地塞米松以及HGF和EGF诱导与胆管上皮形成相关的HNF 6-β的表达。所有三种分子的组合添加与成熟组织学相关，其中肝细胞和胆管谱系是分离的，并且HNF 4仅在肝细胞核中表达。总之，这些结果提供了新的和经常令人惊讶的信息的基因表达的变化，皮质类固醇，HGF和EGF发挥其对肝组织形成的影响。这些结果强调了类器官培养物用于产生组织发生信息的有用性，这是其他培养物或整个动物模型无法获得的。
Corticosteroids, HGF and EGF play important roles in hepatic biology. We have previously shown that these molecules are required for formation of tissue with specific histology in complex organoid cultures. Dexamethasone suppresses growth and induces hepatocyte maturation; HGF and EGF are needed for formation of the non-epithelial elements. All three are needed for formation of the biliary epithelium. The gene expression patterns by which corticosteroids, HGF and EGF mediate their effects in hepatic tissue formation are distinct. These patterns affect many gene families and are described in detail. In terms of main findings, Dexamethasone induces expression of both HNF4 and C/EBP-alpha, essential transcription factors for hepatocyte differentiation. It suppresses hepatocyte growth by suppressing many molecules associated with growth in liver and other tissues, including IL6, CXC-Chemokine receptor, Amphiregulin, COX-2, HIF, etc. HGF and EGF induce all members of the TGF-beta family. They also induced multiple CNS-related genes, probably associated with stellate cells. Dexamethasone, as well as HGF and EGF, induce expression of HNF6-beta, associated with biliary epithelium formation. Combined addition of all three molecules is associated with mature histology in which hepatocyte and biliary lineages are separate and HNF4 is expressed only in hepatocyte nuclei. In conclusion, the results provide new and often surprising information on the gene expression alterations by which corticosteroids, HGF and EGF exert their effects on formation of hepatic tissue. The results underscore the usefulness of the organoid cultures for generating information on histogenesis which cannot be obtained by other culture or whole animal models.
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影响因子：
14.9
作者：
Bailly, A;Torres-Padilla, ME;Weiss, MC
通讯作者：
Weiss, MC
影响因子：
5.3
作者：
Einstein, M;Monga, SPS;Deng, CX
通讯作者：
Deng, CX
影响因子：
4.2
作者：
Buniatian, GH;Hartmann, HJ;Gebhardt, R
通讯作者：
Gebhardt, R
影响因子：
5.6
作者：
BISGAARD, HC;NAGY, P;THORGEIRSSON, SS
通讯作者：
THORGEIRSSON, SS
影响因子：
2.5
作者：
Greenberg, JM;Thompson, FY;Akeson, AL
通讯作者：
Akeson, AL