Liver cell proliferation induced by nafenopin and cyproterone acetate is not associated with increases in activation of transcription factors NF-kappaB and AP-1 or with expression of tumor necrosis factor alpha.
Liver cell proliferation induced by nafenopin and cyproterone acetate is not associated with increases in activation of transcription factors NF-kappaB and AP-1 or with expression of tumor necrosis factor alpha.
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奈非诺平和醋酸环丙孕酮诱导的肝细胞增殖与转录因子 NF-κB 和 AP-1 的激活增加或肿瘤坏死因子 α 的表达无关。
DOI：
10.1002/hep.510250316
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Ledda-Columbano,GM
中科院分区：
文献类型：
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作者：
Menegazzi,M;Carcereri-DePrati,A;Suzuki,H;Shinozuka,H;Pibiri,M;Piga,R;Columbano,A;Ledda-Columbano,GM
我们以前的研究表明，在细胞损失/死亡后发生的代偿性肝再生和由初级有丝分裂原诱导的直接增生之间，立即早期基因和生长因子基因表达的模式不同。在本研究中，在不同类型的细胞增殖过程中，在大鼠肝脏中检查了两种转录因子NF-κB和AP-1的活化、肿瘤坏死因子α（TNF-α）信使RNA（mRNA）的稳态水平以及诱导型一氧化氮合酶（iNOS）的诱导。补偿性再生诱导雄性Wistar大鼠肝部分切除术的三分之二（PH）或CCl 4（2 mL/kg）的坏死剂量，而直接增生诱导的主要有丝分裂原硝酸铅（LN，100 μ mol/kg），醋酸环丙孕酮（CPA，60 mg/kg），或nafenopin（NAF，200 mg/kg）的单次给药。CCl 4处理后的肝再生与TNF-α mRNA稳态水平的增加、NF-κB和AP-1的活化以及iNOS的诱导相关。在LN诱导的增生中观察到NF-κB的强烈和长期活化，但AP-1未被观察到。LN还诱导肝脏TNF-α和iNOS mRNA水平升高。另一方面，由另外两种主要有丝分裂原NAF和CPA诱导的直接增生发生在完全没有TNF-α mRNA水平改变、NF-κB和AP-1活化或iNOS诱导的情况下，尽管NAF后18 - 24小时进入S期的肝细胞数量与PH后相似。这些结果进一步支持了细胞增殖在不存在细胞损失/死亡的情况下发生的细胞凋亡可能是由未知的信号传导途径触发的，该信号传导途径不同于负责PH或细胞坏死后肝细胞从G 0转变为G1的信号传导途径。
Our previous studies have shown a different pattern of immediate early gene and growth factor gene expression between compensatory liver regeneration occurring after cell loss/death and direct hyperplasia induced by primary mitogens. In the present study, modifications in the activation of two transcription factors, NF‐κB and AP‐1; steady‐ state levels of tumor necrosis factor α (TNF‐α) messenger RNA (mRNA); and induction of the inducible nitric oxide synthase (iNOS) were examined in rat liver during different types of cell proliferation. Compensatory regeneration was induced in male Wistar rats by partial hepatectomy of two thirds (PH) or a necrogenic dose of CCl4 (2 mL/kg), whereas direct hyperplasia was induced by a single administration of the primary mitogens lead nitrate (LN, 100 micromol/kg), cyproterone acetate (CPA, 60 mg/kg), or nafenopin (NAF, 200 mg/kg). Liver regeneration after treatment with CCl4 was associated with an increase in steady‐state levels of TNF‐α mRNA, activation of NF‐κB and AP‐1, and induction of iNOS. A strong and prolonged activation of NF‐κB but not of AP‐1 was observed in LN‐induced hyperplasia. LN also induced an increase in hepatic levels of TNF‐α and iNOS mRNA. On the other hand, direct hyperplasia induced by two other primary mitogens, NAF and CPA, occurred in the complete absence of modifications in the hepatic levels of TNF‐α mRNA, activation of NF‐κB and AP‐1, or induction of iNOS, although the number of hepatocytes entering S phase 18 to 24 hours after NAF was similar to that seen after PH. These results add further support to the hypothesis that cell proliferation occurring in the absence of cell loss/death may be triggered by unknown signaling pathways different from those responsible for the transition of hepatocytes from G0 to G1 after PH or cell necrosis.