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Publication : Amelioration in wound healing in diabetic toll-like receptor-4 knockout mice.

First Author  Dasu MR Year  2013
Journal  J Diabetes Complications Volume  27
Issue  5 Pages  417-21
PubMed ID  23773694 Mgi Jnum  J:318980
Mgi Id  MGI:6862185 Doi  10.1016/j.jdiacomp.2013.05.002
Citation  Dasu MR, et al. (2013) Amelioration in wound healing in diabetic toll-like receptor-4 knockout mice. J Diabetes Complications 27(5):417-21
abstractText  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 2weeks 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-alpha concentration and nuclear factor-kappaB (NF-kappaB) 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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