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间质干细胞在体外需要整合素β1 来引导由骨桥蛋白诱导的定向迁移。

Mesenchymal stem cells require integrin β1 for directed migration induced by osteopontin in vitro.

机构信息

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China.

出版信息

In Vitro Cell Dev Biol Anim. 2011 Mar;47(3):241-50. doi: 10.1007/s11626-010-9377-0. Epub 2010 Dec 7.

Abstract

Mesenchymal stem cells (MSCs) are characterized by their ability of self-renewal paired with the capacity to differentiate into multiple mesenchymal cell lineages. Numerous studies have reported beneficial effects of MSCs in tissue repair and regeneration. After in vivo administration, MSCs home to and engraft to injured tissues. However, the molecular mechanisms are not clear. Osteopontin (OPN) has been found to be elevated in response to injury and inflammation and its role on cell mobilization has been studied. Therefore, the facts imply that OPN may contribute to the recruitment of MSCs to the sites of injury. In this study, using transwell assay, we found that rat bone marrow-derived mesenchymal stem cells (rMSCs) migrated towards OPN in a concentration-dependent manner. To further examine the involved molecular mechanisms for OPN-induced rMSCs migration, RT-PCR, and Western blot were used to detect the expressions of integrin β1 and CD44v6, the two receptors of OPN. OPN promoted integrin β1 mRNA and protein expression while CD44v6 mRNA level was not altered. Blockade of integrin β1 also inhibited OPN-induced rMSCs migration, indicating the possible involvement of integrin β1 in OPN-induced migration in rMSCs. Our data have shown for the first time that OPN increases integrin β1 expression in rMSCs and promotes rMSCs migration through the ligation to integrin β1.

摘要

间充质干细胞(MSCs)的特征是自我更新的能力,以及分化为多种间充质细胞谱系的能力。许多研究报告称 MSCs 在组织修复和再生方面具有有益作用。在体内给药后,MSCs 归巢并植入受损组织。然而,其分子机制尚不清楚。骨桥蛋白(OPN)在受到损伤和炎症时会升高,其对细胞动员的作用已被研究。因此,事实表明 OPN 可能有助于将 MSCs 募集到损伤部位。在这项研究中,我们通过 Transwell 测定发现,大鼠骨髓间充质干细胞(rMSCs)以浓度依赖的方式向 OPN 迁移。为了进一步研究 OPN 诱导 rMSCs 迁移所涉及的分子机制,我们使用 RT-PCR 和 Western blot 检测了 OPN 的两个受体整合素 β1 和 CD44v6 的表达。OPN 促进整合素 β1 mRNA 和蛋白表达,而 CD44v6 mRNA 水平没有改变。整合素 β1 的阻断也抑制了 OPN 诱导的 rMSCs 迁移,表明整合素 β1 可能参与了 OPN 诱导的 rMSCs 迁移。我们的数据首次表明,OPN 增加了 rMSCs 中整合素 β1 的表达,并通过与整合素 β1 的结合促进了 rMSCs 的迁移。

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