The effects of TGF-alpha, IL-1beta and PDGF on fibroblast adhesion to ECM-derived matrix and KGF gene expression.

The effects of TGF-alpha, IL-1beta and PDGF on fibroblast adhesion to ECM-derived matrix and KGF gene expression.
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DOI:
10.1016/j.biomaterials.2009.12.018
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发表时间:
2010-03
期刊:
影响因子:
14
通讯作者:
Kao, Weiyuan J.
Kao, Weiyuan J.
中科院分区:
工程技术1区
文献类型:
--
作者:
Wang, Xintong;Waldeck, Heather;Kao, Weiyuan J.

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本研究的目的是阐明外源蛋白调节粘附于不同基质的成纤维细胞中角质形成细胞生长因子(KGF)表达的控制机制,从而为基本的体外细胞信号传导和细胞-生物材料相互作用研究提供见解。建立并使用了细胞保持增殖能力的无血清培养系统。单独添加转化生长因子-α (TGF-α)、白细胞介素-1β (IL-1β) 和血小板源性生长因子-BB (PDGF-BB) 对 KGF 蛋白释放没有影响,然而,添加 IL-1β 会导致 KGF mRNA 转录、细胞内 KGF 蛋白合成和粒细胞巨噬细胞集落刺激因子 (GM-CSF) 释放增加。当成纤维细胞用 IL-1β 和 PDGF-BB 联合处理时,细胞内 KGF 蛋白合成和细胞外释放得到增强,这表明 KGF 合成和释放在很大程度上受到协同机制的调节。表面结合的纤连蛋白衍生配体和单个外源蛋白促进成纤维细胞粘附到半互穿聚合物网络(sIPN),但不刺激 KGF 释放,尽管 KGF mRNA 转录增强。此外,还发现血清调理对 KGF 合成和随后控制 KGF 释放的机制有显着影响。这项研究表明,成纤维细胞释放的 KGF 可能受到涉及转录后和胞吐控制的多种机制的调节,这些机制可能受到血清的存在以及血清从体外细胞环境中去除的方式的影响。
The goal of this study was to elucidate the control mechanisms by which exogenous proteins regulate keratinocyte growth factor (KGF) expression in fibroblasts adhered to differing substrates and thereby provide insights into both fundamental in vitro cell signaling and cell-biomaterial interaction research. A serum-free culture system in which cells maintained their proliferative capacity was established and employed. The addition of transforming growth factor- α (TGF-α), interleukin-1β (IL-1β) and platelet-derived growth factor-BB (PDGF-BB) individually showed no effect on KGF protein release, however, IL-1β addition led to increased KGF mRNA transcription, intracellular KGF protein synthesis, and granulocyte-macrophage colony-stimulating factor (GM-CSF) release. Intracellular KGF protein synthesis and extracellular release were enhanced when fibroblasts were treated with a combination of IL-1β and PDGF-BB which suggests KGF synthesis and release are largely regulated by synergistic mechanisms. Surface-bound fibronectin-derived ligands and individual exogenous proteins promoted fibroblast adhesion to semi-interpenetrating polymer networks (sIPNs) but did not stimulate KGF release despite enhancement of KGF mRNA transcription. Additionally, serum conditioning was found to have a significant impact on KGF synthesis and the subsequent mechanisms controlling KGF release. This study demonstrates that KGF release from fibroblasts is likely regulated by multiple mechanisms involving post-transcriptional and exocytic controls which may be impacted by the presence of serum and how serum is removed from the in vitro cell environment.
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影响因子: --
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