Homologous peptide of connective tissue growth factor ameliorates epithelial to mesenchymal transition of tubular epithelial cells.

Homologous peptide of connective tissue growth factor ameliorates epithelial to mesenchymal transition of tubular epithelial cells.
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结缔组织生长因子的同源肽改善肾小管上皮细胞的上皮到间质的转变。

DOI:
10.1016/j.cyto.2006.10.009
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发表时间:
2006
期刊:
影响因子:
3.8
通讯作者:
Youping Li
Youping Li
中科院分区:
医学3区
文献类型:
--
作者:
Yujun Shi;Z. Tu;Wei Wang;Qing Li;F. Ye;Jin;J. Qiu;Li Zhang;H. Bu;Youping Li

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肾移植失败的标志是肾小管萎缩和间质纤维化。细胞因子结缔组织生长因子(CTGF或CCN2)在肾小管上皮细胞向间充质转化(EMT)过程中起重要作用。CTGF(IRTPKISKPIKFELSG)中有一个独特的结构域与其潜在的整合素受体αvβ3结合。本研究旨在进一步鉴定与该结构域同源的人工合成的十六肽(P2),并研究其对CTGF介导的固相细胞黏附、EMT诱导和大鼠肾NRK-52E细胞纤维化形成的影响。结果表明,P2和重组CTGF均能与NRK-52E细胞结合。与结缔组织生长因子不同,P2对细胞骨架重塑和α-平滑肌肌动蛋白(α-SMA)和E-钙粘素的表达无明显影响,对纤维化的诱导(包括细胞外基质蛋白、I型和IV型胶原在基因和蛋白水平的改变)也没有影响。以上结果表明,P2能较好地结合于NRK-52E细胞表面,并抑制CTGF对EMT诱导和细胞纤维化形成的影响,可能是通过占据CTGF与其潜在受体的结合部位。因此,P2有可能作为一种潜在的抗纤维化药物。
The hallmark of failing renal transplants is tubular atrophy and interstitial fibrosis. The cytokine connective tissue growth factor (CTGF or CCN2) plays an important role in epithelial–mesenchymal transition (EMT) of tubular epithelial cells (TECs). A unique domain within CTGF (IRTPKISKPIKFELSG) which binds to its potential receptor integrin αvβ3 has been identified. This study was carried out to further characterize a synthetic hexadeca-peptide (P2) homologous to this domain and to determine its effect on CTGF-mediated solid phase cell adhesion, EMT induction and fibrogenesis in rat renal NRK-52E cells. Results showed that both P2 and recombinant CTGF bound to NRK-52E cells. Unlike CTGF, P2 had little effect on EMT induction including cytoskeleton remodeling and expression of α-smooth muscle actin (α-SMA) and E-cadherin, nor did it have effect on fibrogenic induction including alternation of extracellular matrix (ECM) proteins, collagen type I and IV at gene and protein levels. All data showed that P2 bound preferably on the surface of NRK-52E cells and inhibited the effect of CTGF on EMT induction and cell fibrogenesis, probably by occupying the binding sites of CTGF within its potential receptors. Therefore, P2 may be used as a potential anti-fibrotic agent.
DOI: 10.1091/mbc.e05-08-0767
发表时间: 2006-04-01
影响因子: 3.3
作者:
Medici, D;Hay, ED;Goodenough, DA
通讯作者: Goodenough, DA
DOI: 10.1111/j.1399-3046.2004.00182.x
发表时间: 2004-08-01
影响因子: 1.3
作者:
Salifu, MO;Nicastri, AD;Friedman, EA
通讯作者: Friedman, EA
DOI: 10.1182/blood.v99.12.4457
发表时间: 2002-06-15
期刊: BLOOD
影响因子: 20.3
作者:
Schober, JM;Chen, NY;Lam, SCT
通讯作者: Lam, SCT