title: Increased expression of endosomal members of toll-like receptor family abrogates wound healing in patients with type 2 diabetes mellitus.
abstract: The inflammatory phase of wound healing cascade is an important determinant of the fate of the wound. Acute inflammation is necessary to initiate proper wound healing, while chronic inflammation abrogates wound healing. Different endosomal members of toll-like receptor (TLR) family initiate inflammatory signalling via a range of different inflammatory mediators such as interferons, internal tissue damaged-associated molecular patterns (DAMPs) and hyperactive effector T cells. Sustained signalling of TLR9 and TLR7 contributes to chronic inflammation by activating the plasmacytoid dendritic cells. Diabetic wounds are also characterised by sustained inflammatory phase. The objective of this study was to analyse the differential expression of endosomal TLRs in human diabetic wounds compared with control wounds. We analysed the differential expression of TLR7 and TLR9 both at transcriptional and translational levels in wounds of 84 patients with type 2 diabetes mellitus (T2DM) and 6 control subjects without diabetes using quantitative real-time polymerase chain reaction (RT-PCR), western blot and immunohistochemistry. TLR7 and TLR9 were significantly up-regulated in wounds of the patients with T2DM compared with the controls and were dependent on the infection status of the diabetic wounds, and wounds with microbial infection exhibited lower expression levels of endosomal TLRs. Altered endosomal TLR expression in T2DM subjects might be associated with wound healing impairment.
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 General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Department of Pathology, Indian Railway Cancer Hospital and Research Center, N.E.R., Varanasi, 221002, India.
authors.forename: Gyanendra
authors.initials: G
authors.lastname: Mohan
authors.affiliation: Department of Pathology, Indian Railway Cancer Hospital and Research Center, 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. skiran@bhu.ac.in.
authors.forename: Kiran
authors.initials: K
authors.lastname: Singh
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism*; D017719:Diabetic Foot / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9
keywords: Diabetic foot ulcer; T2DM; TLR7; TLR9; Toll-like receptors; Wound healing impairment