Amelioration in wound healing in diabetic toll-like receptor-4 knockout mice.
Amelioration in wound healing in diabetic toll-like receptor-4 knockout mice.
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DOI：
10.1016/j.jdiacomp.2013.05.002
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发表时间：
2013-09
影响因子：
3
通讯作者：
Jialal I
中科院分区：
文献类型：
--
作者：
Dasu MR;Jialal I
Toll样受体4（TLR 4）是一种病原体识别受体，在炎症、组织损伤、糖尿病及其并发症中发挥重要作用。该研究的目的是检查TLR 4表达和活化对糖尿病伤口中观察到的长期炎症的贡献。使用链脲佐菌素（STZ）在雄性C57 BL/6 J和TLR 4敲除（KO）小鼠中诱导糖尿病，并以匹配的非糖尿病小鼠作为对照。在小鼠中持续高血糖2周后，在背部无菌地制作全层切除伤口。对总RNA和蛋白质进行实时PCR和蛋白质印迹分析。使用数字平面测量法测量伤口尺寸。糖尿病小鼠创面中TLR 4 mRNA和蛋白表达较非糖尿病小鼠明显增加（P<0.05）。与非糖尿病伤口相比，糖尿病伤口中IL-6、TNF-α浓度和核因子-κB（NF-κB）活化增加，并且在糖尿病TLR 4 KO小鼠中TLR 4敲除促进伤口愈合并减少炎症。总的来说，我们的研究结果表明，增加的TLR 4 mRNA和蛋白表达和活化有助于糖尿病伤口中的炎症延长，并且TLR 4的缺乏可能导致炎症减少和伤口愈合改善。
Toll-like receptor-4 (TLR4) is a sentinel pathogen recognition receptor with a pivotal role in inflammation, tissue injury, diabetes and its complications. The aim of the study was to examine the contribution of TLR4 expression and activation to the prolonged inflammation observed in diabetic wounds. Diabetes was induced in male C57BL/6J and TLR4 knockout (KO) mice using streptozotocin (STZ) with matching non-diabetic mice as control. After 2 weeks of persistent hyperglycemia in the mice, full-thickness excision wounds were made on the backs aseptically. Total RNA and protein were subjected to real-time PCR and western blot analyses. Wound sizes were measured using digital planimetry. TLR4 mRNA and protein expression increased significantly in wounds of diabetic mice compared with non-diabetic mice (P<0.05). IL-6, TNF-α concentration and nuclear factor-κB (NF-κB) activation were increased in diabetic wounds compared to non-diabetic wounds and knockout of TLR4 alleviates wound healing and decreases inflammation in diabetic TLR4 KO mice. Collectively, our findings show that increased TLR4 mRNA and protein expression and activation contribute to the prolonged inflammation in the diabetic wounds and that absence of TLR4 may result in decreased inflammation and improved wound healing.
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影响因子：
16.2
作者：
Ghanim H;Abuaysheh S;Sia CL;Korzeniewski K;Chaudhuri A;Fernandez-Real JM;Dandona P
通讯作者：
Dandona P
影响因子：
3.3
作者：
Ramirez, Sandra Rosa;Dasu, Mohan Ravi Krishna
通讯作者：
Dasu, Mohan Ravi Krishna
影响因子：
7.7
作者：
Cani, Patrice D.;Bibiloni, Rodrigo;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
4.8
作者：
Taylor, KR;Trowbridge, JM;Gallo, RL
通讯作者：
Gallo, RL
影响因子：
15.9
作者：
Shi, Hang;Kokoeva, Maia V.;Flier, Jeffrey S.
通讯作者：
Flier, Jeffrey S.