The gene encoding rat insulinlike growth factor-binding protein 1 is rapidly and highly induced in regenerating liver

The gene encoding rat insulinlike growth factor-binding protein 1 is rapidly and highly induced in regenerating liver
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编码大鼠胰岛素样生长因子结合蛋白1的基因在肝脏再生过程中被快速且高度诱导

DOI:
10.1128/mcb.11.3.1393-1401.1991
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发表时间:
1991
影响因子:
5.3
通讯作者:
R. Taub
R. Taub
中科院分区:
生物学2区
文献类型:
--
作者:
K. Mohn;A. Melby;D. Tewari;T. Laz;R. Taub

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肝脏是一种上皮样器官,可以在部分肝切除术后再生。虽然它主要由肝细胞组成,但它具有复杂的多细胞结构,这意味着在再生过程中必须存在细胞间通讯。与其他受丝裂原刺激的细胞一样,在缺乏蛋白质合成的情况下诱导的即时早期生长反应基因可能在再生过程中发挥重要的调节作用。通过对再生肝脏cDNA文库的差异筛选,我们发现肝脏再生中表达水平最高的直接早期基因之一编码了低分子胰岛素样生长因子(IGF)结合蛋白(IGFBP-1)的大鼠同源基因。该蛋白与增强IGF对组织的有丝分裂作用有关。IGFBP-1基因的诱导是转录介导的,对肝脏再生具有特异性,因为该基因在丝裂原刺激的成纤维细胞中不表达。IGFBP-1在糖尿病等低胰岛素条件下表达增加,我们发现胰岛素治疗H35大鼠肝癌细胞,在诱导增殖的同时,也会导致IGFBP-1基因的转录和表达迅速下降,这表明了IGFBP-1表达的复杂调控。值得注意的是,IGFBP-1 mRNA在胎鼠肝脏中含量丰富,这意味着它参与了正常肝脏的生长发育。尽管再生的肝细胞继续产生IGF-I,但在肝切除术后的前24小时内,我们没有检测到IGF-I受体mRNA。然而,一些igfbp可能独立于IGF-I受体而增强IGF-I的活性。因此,IGF-1和igfbp可能通过IGF-1或新的受体与肝细胞或非实质肝细胞相互作用。通过这种方式,IGFBP-I和IGF-I可以旁分泌和/或自分泌的方式在肝脏再生过程中维持正常的肝脏结构。
The liver is an epithelioid organ that can regenerate following partial hepatectomy. Although it is composed mainly of hepatocytes, it has a complex, multicellular architecture, implying that intercellular communications must exist during regeneration. As in other mitogen-stimulated cells, immediate-early growth response genes induced in the absence of prior protein synthesis are likely to play an important regulatory role in the regenerative process. Through differential screening of regenerating liver cDNA libraries, we found that one of the most highly expressed immediate-early genes in liver regeneration encodes the rat homolog of the low-molecular-weight insulinlike growth factor (IGF)-binding protein (IGFBP-1). This protein has been implicated in enhancing the mitogenic effect of IGF on tissues. IGFBP-1 gene induction is transcriptionally mediated and specific to regenerating liver, as the gene is not expressed in mitogen-stimulated fibroblasts. IGFBP-1 expression has been shown to increase under low-insulin conditions such as diabetes, and the complex regulation of expression is indicated by our finding that insulin treatment of H35 rat hepatoma cells, which induces proliferation, also causes a rapid decrease in transcription and expression of the IGFBP-1 gene. Of note, IGFBP-1 mRNA is abundant in fetal rat liver, implying that it participates in normal liver growth and development. Although regenerating liver cells continue to produce IGF-I, we did not detect IGF-I receptor mRNA during the first 24 h after hepatectomy. However, some IGFBPs may act to enhance the activity of IGF-I independently of IGF-I receptors. Thus, IGF-1 and IGFBPs may interact with hepatocytes or nonparenchymal liver cells, through either IGF-I or novel receptors. In this way, IGFBP-I and IGF-I could act in a paracrine and/or autocrine fashion in maintaining normal liver architecture during regeneration.
DOI: 10.1126/science.2876518
发表时间: 1986-10-17
期刊: SCIENCE
影响因子: 56.9
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发表时间: 1989
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作者:
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DOI: --
发表时间: 1990
期刊: The Journal of biological chemistry
影响因子: --
作者:
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DOI: --
发表时间: 1989
期刊: Laboratory investigation; a journal of technical methods and pathology
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