Secretome analysis of in vitro aged human mesenchymal stem cells reveals IGFBP7 as a putative factor for promoting osteogenesis.
Secretome analysis of in vitro aged human mesenchymal stem cells reveals IGFBP7 as a putative factor for promoting osteogenesis.
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DOI：
10.1038/s41598-018-22855-z
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发表时间：
2018-03-15
影响因子：
4.6
通讯作者：
Rodríguez CI
中科院分区：
文献类型：
--
作者：
Infante A;Rodríguez CI
衰老是一个复杂的生物学过程，涉及到多种机制，具有不同的调节水平。已知衰老细胞分泌衰老相关蛋白，其对周围细胞施加负面影响。骨髓间充质干细胞（Mesenchymal stem cells，MSCs）是骨、软骨和脂肪组织的共同祖细胞，在许多生物学过程中可分泌多种具有旁分泌和自分泌功能的生物活性蛋白。在这份报告中，我们研究了分泌因子（分泌组）从人骨髓间充质干细胞（hMSCs）和hMSCs衍生的脂肪细胞诱导积累前核纤层蛋白A，核纤层蛋白的不成熟形式称为核纤层蛋白A，已知诱导人类和小鼠模型的过早衰老综合征。从两种不同的技术，抗体阵列和LS-MS的蛋白质组学分析表明，前层蛋白A在hMSCs中的积累促进了差异分泌的因子，以前确定为分泌的hMSCs进行成骨。此外，该分泌蛋白能够调节正常hMSCs在体外的成骨。最后，我们发现，这种人衰老的体外干细胞模型，IGFBP-7，是一种成骨因子，在成骨过程中的hMSCs的活力是必不可少的过表达分泌的因素之一。
Aging is a complex biological process, which involves multiple mechanisms with different levels of regulation. Senescent cells are known to secrete senescence-associated proteins, which exert negative influences on surrounding cells. Mesenchymal stem cells (MSCs), the common progenitors for bone, cartilage and adipose tissue (which are especially affected tissues in aging), are known to secrete a broad spectrum of biologically active proteins with both paracrine and autocrine functions in many biological processes. In this report, we have studied the secreted factors (secretome) from human MSCs (hMSCs) and hMSCs-derived adipocytes which were induced to accumulate prelamin A, the immature form of the nuclear lamina protein called Lamin A, known to induce premature aging syndromes in humans and in murine models. Proteomic analysis from two different techniques, antibody arrays and LS-MS, showed that prelamin A accumulation in hMSCs promotes the differential secretion of factors previously identified as secreted by hMSCs undergoing osteogenesis. Moreover, this secretome was able to modulate osteogenesis of normal hMSCs in vitro. Finally, we found that one of the overexpressed secreted factors of this human aging in vitro stem cell model, IGFBP-7, is an osteogenic factor, essential for the viability of hMSCs during osteogenesis.
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影响因子：
8
作者：
Pen, A.;Moreno, M. J.;Stanimirovic, D. B.
通讯作者：
Stanimirovic, D. B.
影响因子：
9
作者：
Blondel S;Egesipe AL;Picardi P;Jaskowiak AL;Notarnicola M;Ragot J;Tournois J;Le Corf A;Brinon B;Poydenot P;Georges P;Navarro C;Pitrez PR;Ferreira L;Bollot G;Bauvais C;Laustriat D;Mejat A;De Sandre-Giovannoli A;Levy N;Bifulco M;Peschanski M;Nissan X
通讯作者：
Nissan X
影响因子：
82.9
作者：
Farr JN;Xu M;Weivoda MM;Monroe DG;Fraser DG;Onken JL;Negley BA;Sfeir JG;Ogrodnik MB;Hachfeld CM;LeBrasseur NK;Drake MT;Pignolo RJ;Pirtskhalava T;Tchkonia T;Oursler MJ;Kirkland JL;Khosla S
通讯作者：
Khosla S
影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
--
作者：
Chiellini, Chiara;Cochet, Olivia;Amri, Ez-Zoubir
通讯作者：
Amri, Ez-Zoubir