Genetic and epigenetic alterations in Toll like receptor 2 and wound healing impairment in type 2 diabetes patients

• Published in: Journal of diabetes and its complications 2015-03, Vol.29 (2), p.222-229
• Main Authors: Singh, Kanhaiya, Agrawal, Neeraj K, Gupta, Sanjeev K, Mohan, Gyanendra, Chaturvedi, Sunanda, Singh, Kiran
• Format: Article
• Language: English
• Subjects: Bacteria; Biopsy; Case-Control Studies; CpG Islands; Cytokines; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetic Foot - immunology; Diabetic Foot - metabolism; Diabetic Foot - pathology; Diabetic Foot - physiopathology; DNA Methylation; Endocrinology & Metabolism; Epigenesis, Genetic; Epigenetics; Expression; Family medical history; Female; Foot diseases; Gene expression; Gene Expression Regulation; Hospitals; Hospitals, University; Humans; Immune system; Immunity, Innate; Immunohistochemistry; Infections; Laboratories; Male; Middle Aged; Promoter Regions, Genetic; Proteins; RNA, Messenger - metabolism; Scholarships & fellowships; Science; Severity of Illness Index; TLR2; Toll like receptor; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Transcription factors; Type 2 diabetes; Wound Healing; Wound healing impairment
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2014.11.015

Abstract 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.