PMID- 25541252 OWN - NLM STAT- MEDLINE DCOM- 20151110 LR - 20150217 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 29 IP - 2 DP - 2015 Mar TI - Genetic and epigenetic alterations in Toll like receptor 2 and wound healing impairment in type 2 diabetes patients. PG - 222-9 LID - S1056-8727(14)00369-9 [pii] LID - 10.1016/j.jdiacomp.2014.11.015 [doi] AB - AIM: Persistent hyperglycemic microenvironment in type 2 diabetes mellitus (T2DM) leads to the development of secondary complications like wound healing impairment. Proper co-ordination of innate immune system plays an integral role in wound healing. Toll like receptors (TLRs) are prominent contributors for the induction of the innate immune and inflammation response. TLR2 is an important extracellular member in mammalian TLR family and has been shown to be a potent player in the wound healing mechanism. METHODS: Expressional status of TLR2 was seen in wounds of T2DM cases with respect to the severity of wounds in 110 human lower extremity wounds. The methylation status of TLR2 promoter was also examined. RESULTS: Although TLR2 transcripts were downregulated in T2DM wounds compared to control, their levels tend to increase with the severity of T2DM wounds. The methylation status of TLR2 gene promoter was not significantly different among different grades of wounds in T2DM subjects. The CpG sites investigated were totally or partially methylated in majority of DFU cases. CONCLUSION: TLR2 down regulation in wounds of T2DM patients compared to non diabetic patients may lead to development of non healing chronic ulcers in them. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Singh, Kanhaiya AU - Singh K AD - Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi-221005, India. FAU - Agrawal, Neeraj K AU - Agrawal NK AD - Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India. FAU - Gupta, Sanjeev K AU - Gupta SK AD - Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India. FAU - Mohan, Gyanendra AU - Mohan G AD - Indian Railway Cancer Hospital and Research Centre, N.E.R., Varanasi- 221002, India. FAU - Chaturvedi, Sunanda AU - Chaturvedi S AD - Indian Railway Cancer Hospital and Research Centre, N.E.R., Varanasi- 221002, India. FAU - Singh, Kiran AU - Singh K AD - Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi-221005, India. Electronic address: singhk4@rediffmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141203 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (RNA, Messenger) RN - 0 (TLR2 protein, human) RN - 0 (Toll-Like Receptor 2) SB - IM MH - Biopsy MH - Case-Control Studies MH - CpG Islands MH - *DNA Methylation MH - Diabetes Mellitus, Type 2/*complications MH - Diabetic Foot/immunology/*metabolism/pathology/physiopathology MH - Epigenesis, Genetic MH - Female MH - *Gene Expression Regulation MH - Hospitals, University MH - Humans MH - Immunity, Innate MH - Immunohistochemistry MH - Male MH - Middle Aged MH - *Promoter Regions, Genetic MH - RNA, Messenger/metabolism MH - Severity of Illness Index MH - Toll-Like Receptor 2/genetics/*metabolism MH - *Wound Healing OTO - NOTNLM OT - Epigenetics OT - Expression OT - TLR2 OT - Toll like receptor OT - Type 2 diabetes OT - Wound healing impairment EDAT- 2014/12/30 06:00 MHDA- 2015/11/11 06:00 CRDT- 2014/12/27 06:00 PHST- 2014/08/04 00:00 [received] PHST- 2014/11/26 00:00 [revised] PHST- 2014/11/27 00:00 [accepted] PHST- 2014/12/27 06:00 [entrez] PHST- 2014/12/30 06:00 [pubmed] PHST- 2015/11/11 06:00 [medline] AID - S1056-8727(14)00369-9 [pii] AID - 10.1016/j.jdiacomp.2014.11.015 [doi] PST - ppublish SO - J Diabetes Complications. 2015 Mar;29(2):222-9. doi: 10.1016/j.jdiacomp.2014.11.015. Epub 2014 Dec 3.