Abi3bp is a multifunctional autocrine/paracrine factor that regulates mesenchymal stem cell biology.

Abi3bp is a multifunctional autocrine/paracrine factor that regulates mesenchymal stem cell biology.
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DOI:
10.1002/stem.1416
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发表时间:
2013-08
期刊:
影响因子:
5.2
通讯作者:
Dzau, Victor J.
Dzau, Victor J.
中科院分区:
医学2区
文献类型:
--
作者:
Hodgkinson, Conrad P.;Naidoo, Vinogran;Patti, Karl G.;Gomez, Jose A.;Schmeckpeper, Jeffrey;Zhang, Zhiping;Davis, Bryce;Pratt, Richard E.;Mirotsou, Maria;Dzau, Victor J.

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间充质干细胞(MSCs)移植到受损心肌通过旁分泌机制促进修复。我们先前已经证明过表达AKT 1的MSC(Akt-MSC)表现出增强的心脏修复特性。在这项研究中,我们研究了Abi 3bp与MSC生物学的相关性。Abi 3bp形成细胞外沉积物,其表达受Akt 1和泛素介导的降解控制。Abi 3bp敲低/敲除稳定了局灶性粘连并促进了应力纤维形成。此外,来自Abi 3bp敲除小鼠的MSC在成骨和成脂分化方面显示出严重缺陷。Abi 3bp的敲除或稳定敲除增加MSC和Akt-MSC增殖,通过细胞周期蛋白-d1、ERK 1/2和Src促进S期进入。Abi 3bp与整合素β1结合后,Src与桩蛋白结合,抑制细胞增殖。在体内,Abi 3bp敲除增加了骨髓、肺和肝中的MSC数量和增殖。总之,我们已经确定了一种新的细胞外基质蛋白质所必需的开关从增殖到分化的间充质干细胞。
Mesenchymal stem cells (MSCs) transplanted into injured myocardium promote repair through paracrine mechanisms. We have previously shown that MSCs overexpressing AKT1 (Akt-MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigated the relevance of Abi3bp towards MSC biology. Abi3bp formed extracellular deposits with expression controlled by Akt1 and ubiquitin-mediated degradation. Abi3bp knockdown/knockout stabilized focal adhesions and promoted stress-fiber formation. Furthermore, MSCs from Abi3bp knockout mice displayed severe deficiencies in osteogenic and adipogenic differentiation. Knockout or stable knockdown of Abi3bp increased MSC and Akt-MSC proliferation, promoting S-phase entry via cyclin-d1, ERK1/2 and Src. Upon Abi3bp binding to integrin-β1 Src associated with paxillin which inhibited proliferation. In vivo, Abi3bp knockout increased MSC number and proliferation in bone marrow, lung, and liver. In summary, we have identified a novel extracellular matrix protein necessary for the switch from proliferation to differentiation in MSCs.
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