Original Article Anti-oxidant pathways are stimulated by mesenchymal stromal cells in renal repair after ischemic injury
Original Article Anti-oxidant pathways are stimulated by mesenchymal stromal cells in renal repair after ischemic injury
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DOI：
10.3109/14653249.2011.613927
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发表时间：
2012-02-01
期刊：
影响因子：
4.5
通讯作者：
Gobe, Glenda C.
中科院分区：
文献类型：
--
作者：
Liu, Hongyan;Mctaggart, Steven J.;Gobe, Glenda C.
背景目标。缺血再灌注损伤是急性肾功能衰竭的常见原因。骨髓（BM）来源的间充质干细胞（MSC）肾IR后交付肾保护，但知识的保护机制仍在发展中。本研究分析了MSC的保护性分子机制，特别是与调节氧化应激有关的机制。方法.在体内和体外模型的肾IR进行了分析与MSC。在体内，成年雄性Sprague-Dawley大鼠接受40分钟的单侧肾脏IR。IR后24小时给予大鼠BM来源的MSC（IR + MSC）。其他组有IR但无MSC，或MSC但无缺血（所有组n = 4）。细胞凋亡，炎症，氧化应激和修复信号转导分子或生长因子进行了研究后4天IR。在体外，MSC对氧化应激（0.4 mM过氧化氢）的保护进行了研究，使用大鼠肾小管上皮细胞（NRK 52 E）与或不与MSC在共培养（组织培养trans-well插入），随后进行类似的分析，在体内的调查。结果在体内，IR + MSC动物的肾脏具有显著增加的细胞增殖/再生（细胞增殖细胞核抗原阳性，表皮生长因子表达），增加的血红素加氧酶-1（改善的细胞存活，抗氧化剂）和减少的8-OHdG（减少的氧化应激）。在体外，用氧化应激递送的MSC显着减少细胞凋亡和Bax（促细胞凋亡蛋白），并增加有丝分裂和磷酸化ERK 1/2，从而最大限度地减少损伤结果并最大限度地提高氧化应激后的再生效果。结论. MSC在IR中的益处主要是促再生，有时是抗凋亡，并且确定了新的抗氧化机制。
Background aims. Ischemia-reperfusion (IR) injury is a common cause of acute renal failure. Bone marrow (BM)-derived mesenchymal stromal cells (MSC) delivered after renal IR are renoprotective, but knowledge of the protective mechanism is still in development. This investigation analyzed the protective molecular mechanisms of MSC, in particular relating to modulated oxidative stress. Methods. In vivo and in vitro models of renal IR were analyzed with and without MSC. In vivo, adult male Sprague-Dawley rats were subjected to 40-min unilateral renal IR. Rat BM-derived MSC were administered at 24 h post-IR (IR + MSC). Other groups had IR but no MSC, or MSC but no ischemia (all groups n = 4). Apoptosis, inflammation, oxidative stress and reparative signal transduction molecules or growth factors were studied 4 days post-IR. In vitro, protection by MSC against oxidative stress (0.4 mM hydrogen peroxide) was investigated using rat renal tubular epithelial cells (NRK52E) with or without MSC in co-culture (tissue culture trans-well inserts), followed by similar analyses to the in vivo investigation. Results. In vivo, kidneys of IR + MSC animals had significantly increased cell proliferation/regeneration (cells positive for proliferating cell nuclear antigen, expression of epidermal growth factor), increased heme-oxygenase-1 (improved cell survival, anti-oxidant) and decreased 8-OHdG (decreased oxidative stress). In vitro, MSC delivered with oxidative stress significantly decreased apoptosis and Bax (pro-apoptotic protein), and increased mitosis and phospho-ERK1/2, thereby minimizing the damaging outcome and maximizing the regenerative effect after oxidative stress. Conclusions. The benefits of MSC, in IR, were primarily pro-regenerative, sometimes anti-apoptotic, and novel anti-oxidant mechanisms were identified.