Bone marrow-derived mesenchymal stromal cells (MSCs) have been wildly applied to cell-based strategies for tissue engineering and regenerative medicine; however, they have to undergo the senescence process and thus appeared to be less therapeutic effective. HMGA2, a protein belonged to high mobility group A (HMGA) family, exhibits an inverse expression level related to embryonic development and acts as a developmental regulator in stem cell self-renewal progression. Therefore, we performed senescence-associated β-galactosidase (SA-β-gal) staining, transwell assay, to examine the changes of MSCs in different stages and then over-expressed HMGA2 in MSCs by lentivirus transfection. We found the percentage of SA-β-gal staining positive cells in MSCs from 24-month-old Sprague-Dawley (SD) rats (O-MSCs) was significantly higher compared with MSCs from 2-week-old SD rats (Y-MSCs), and the expression levels of P21 and P53, two senescence-related molecules, were also significantly up-regulated in O-MSCs than in Y-MSCs. In contrast, the HMGA2 expression level in O-MSCs was dramatically down-regulated in contrast to Y-MSCs. In additional, the migration ability in O-MSCs was significantly attenuated than in Y-MSCs. After successfully over-expressed HMGA2 in O-MSCs, the percentage of SA-β-gal staining positive cells and the expression levels of P21 and P53 were reduced, and the migration ability was improved compared with O-MSCs without treatment. Further, mRNA sequencing analysis revealed that overexpression of HMGA2 changed the expression of genes related to cell proliferation and senescence, such as Lyz2, Pf4, Rgs2, and Mstn. Knockdown of Rgs2 in HMGA2 overexpression O-MSCs could antagonize the protective effect of HMGA2 in the senescence process of O-MSCs.

中文翻译：

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HMGA2在骨髓间充质基质细胞衰老过程中的保护作用。

骨髓间充质基质细胞（MSCs）已被广泛应用于组织工程和再生医学的基于细胞的策略；然而，它们必须经历衰老过程，因此似乎治疗效果较差。HMGA2是高迁移率A组（HMGA）家族​​的一种蛋白质，具有与胚胎发育相关的逆表达水平，并在干细胞自我更新过程中起发育调节作用。因此，我们进行了衰老相关的β-半乳糖苷酶（SA-β-gal）染色，transwell分析，以检查MSC在不同阶段的变化，然后通过慢病毒转染在MSC中过表达HMGA2。我们发现24月龄Sprague-Dawley（SD）大鼠（O-MSC）的MSC中SA-β-gal染色阳性细胞的百分比显着高于2周龄SD大鼠的MSC（Y- MSCs，以及两个衰老相关分子P21和P53的表达水平，在O-MSCs中也明显高于在Y-MSCs中。相反，与Y-MSC相比，O-MSC中的HMGA2表达水平显着下调。另外，与Y-MSC相比，O-MSC中的迁移能力显着减弱。与未处理的O-MSC相比，成功地在O-MSC中过表达HMGA2后，SA-β-gal染色阳性细胞的百分比以及P21和P53的表达水平降低，迁移能力得到改善。进一步，mRNA测序分析表明，HMGA2的过表达改变了与细胞增殖和衰老相关的基因的表达，例如Lyz2，Pf4，Rgs2和Mstn。在HMGA2过表达的O-MSC中敲除Rgs2可以拮抗HMGA2在O-MSC衰老过程中的保护作用。