title: Genetic and epigenetic alterations in Toll like receptor 2 and wound healing impairment in type 2 diabetes patients.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  TLR2 down regulation in wounds of T2DM patients compared to non diabetic patients may lead to development of non healing chronic ulcers in them.
authors.affiliation: Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi-221005, India.
authors.forename: Kanhaiya
authors.initials: K
authors.lastname: Singh
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India.
authors.forename: Neeraj K
authors.initials: NK
authors.lastname: Agrawal
authors.affiliation: Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India.
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Indian Railway Cancer Hospital and Research Centre, N.E.R., Varanasi- 221002, India.
authors.forename: Gyanendra
authors.initials: G
authors.lastname: Mohan
authors.affiliation: Indian Railway Cancer Hospital and Research Centre, N.E.R., Varanasi- 221002, India.
authors.forename: Sunanda
authors.initials: S
authors.lastname: Chaturvedi
authors.affiliation: Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi-221005, India. Electronic address: singhk4@rediffmail.com.
authors.forename: Kiran
authors.initials: K
authors.lastname: Singh
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D017719:Diabetic Foot / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006785:Hospitals, University; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D012333:RNA, Messenger; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2
keywords: Epigenetics; Expression; TLR2; Toll like receptor; Type 2 diabetes; Wound healing impairment