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Research Article

人脂肪干细胞分泌的肝细胞生长因子抑制肥厚性瘢痕成纤维细胞的纤维化

卷 20, 期 7, 2020

页: [558 - 571] 页: 14

弟呕挨: 10.2174/1566524020666200106095745

价格: $65

摘要

目的：研究脂肪干细胞（ADSCs）对增生性瘢痕成纤维细胞（HSFs）纤维化的影响及其具体机制。 背景：据报道，在共培养实验中，ADSC可以减少胶原蛋白的产生和成纤维细胞的增殖。来自脂肪干细胞的条件培养基（ADSCs-CM）通过降低兔耳疤痕模型中І型胶原（Col1）和α-平滑肌肌动蛋白（α-SMA）的表达，成功抑制了纤维化。肝细胞生长因子（HGF）是ADSCs-CM中的主要生长因子，已显示可逆转各种纤维化疾病中的纤维化。 目的：检验ADSC通过分泌HGF抑制HSF纤维化的假说。 方法：用含0％，10％，50％和100％ADSCs-CM浓度的DMEM处理HSF。通过细胞生存力测定法确定ADSCs-CM对生存力的影响，并通过天狼星红染色检查HSF中胶原蛋白的产生。分别检测纤维化和降解蛋白的表达和分泌。在测量ADSCs-CM中的HGF浓度后，用50％ADSCs-CM或HGF处理相同数量的HSF。用山羊抗人HGF抗体中和ADSCs-CM中的HGF活性。 结果：结果表明，ADSCs-CM剂量依赖性地降低了HSF中的细胞活力，纤维化分子表达和金属蛋白酶-1（TIMP-1）的组织抑制剂，并显着增加了基质金属蛋白酶-1（MMP-1）的表达。 ADSCs-CM也以剂量依赖的方式抑制胶原蛋白的产生以及І和Ⅲ型胶原蛋白的比例（Col1 / Col3）。用50％ADSCs-CM或HGF（1 ng / ml）培养HSF时，在基因表达和蛋白质分泌中观察到类似趋势。两组均添加HGF抗体可使蛋白表达和分泌恢复至基础水平，但对对照组的纤维化因子没有明显影响。 结论：我们的研究结果表明，脂肪干细胞分泌的HGF可有效抑制增生性瘢痕成纤维细胞中与纤维化相关的因子并调节细胞外基质（ECM）重塑。

关键词: 脂肪源性干细胞(ADSCs)、肥厚性瘢痕成纤维细胞(HSFS)、ADSCs条件培养基(ADSCs-CM)、肝细胞生长因子(HGF)、胶原、细胞外基质。

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