Adenosine accelerates the healing of diabetic ischemic ulcers by improving autophagy of endothelial progenitor cells grown on a biomaterial.
Adenosine accelerates the healing of diabetic ischemic ulcers by improving autophagy of endothelial progenitor cells grown on a biomaterial.
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腺苷通过改善在生物材料上生长的内皮祖细胞的自噬来加速糖尿病缺血性溃疡的愈合。
DOI：
10.1038/srep11594
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发表时间：
2015-06-25
影响因子：
4.6
通讯作者：
Zhu C
中科院分区：
文献类型：
--
作者：
Chen W;Wu Y;Li L;Yang M;Shen L;Liu G;Tan J;Zeng W;Zhu C
内皮祖细胞（EPCs）种植在生物材料上可有效促进糖尿病缺血创面愈合。然而，移植的EPCs的功能受到高糖和缺血微环境的负面影响。我们的实验表明，EPC自噬被抑制，线粒体膜电位（MMP）在糖尿病患者增加，而腺苷治疗降低能量需求，并增加EPCs的自噬水平。在动物实验中，我们将一种种植有EPCs的生物材料移植到糖尿病伤口表面，发现腺苷刺激的EPCs有效地促进伤口愈合。在腺苷刺激组中也观察到移植细胞的微血管生成和存活增加。有趣的是，我们的研究表明，腺苷增加了移植到生物材料上的EPC的自噬，并在48和96小时维持EPC的存活。此外，我们观察到腺苷通过增加自噬水平来诱导EPC分化。总之，我们的研究表明，腺苷刺激的内皮祖细胞接种到生物材料上显着改善糖尿病小鼠的伤口愈合;从机制上讲，腺苷可能通过增加高葡萄糖抑制的EPC自噬和维持细胞能量代谢来维持EPC的存活和分化。
Endothelial progenitor cells (EPCs) seeded on biomaterials can effectively promote diabetic ischemic wound healing. However, the function of transplanted EPCs is negatively affected by a high-glucose and ischemic microenvironment. Our experiments showed that EPC autophagy was inhibited and mitochondrial membrane potential (MMP) was increased in diabetic patients, while adenosine treatment decreased the energy requirements and increased the autophagy levels of EPCs. In animal experiments, we transplanted a biomaterial seeded with EPCs onto the surface of diabetic wounds and found that adenosine-stimulated EPCs effectively promoted wound healing. Increased microvascular genesis and survival of the transplanted cells were also observed in the adenosine-stimulated groups. Interestingly, our study showed that adenosine increased the autophagy of the transplanted EPCs seeded onto the biomaterial and maintained EPC survival at 48 and 96 hours. Moreover, we observed that adenosine induced EPC differentiation through increasing the level of autophagy. In conclusion, our study indicated that adenosine-stimulated EPCs seeded onto a biomaterial significantly improved wound healing in diabetic mice; mechanistically, adenosine might maintain EPC survival and differentiation by increasing high glucose-inhibited EPC autophagy and maintaining cellular energy metabolism.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
20.1
作者：
Barcelos LS;Duplaa C;Kränkel N;Graiani G;Invernici G;Katare R;Siragusa M;Meloni M;Campesi I;Monica M;Simm A;Campagnolo P;Mangialardi G;Stevanato L;Alessandri G;Emanueli C;Madeddu P
通讯作者：
Madeddu P
影响因子：
14
作者：
Min, BM;Lee, G;Park, WH
通讯作者：
Park, WH
影响因子：
8.2
作者：
Gershater, M. A.;Londahl, M.;Apelqvist, J.
通讯作者：
Apelqvist, J.
影响因子：
158.5
作者：
Duckworth, William;Abraira, Carlos;Huang, Grant D.
通讯作者：
Huang, Grant D.