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Title: Genetic Analysis of Impairment of Diabetic Wound Healing
Researcher: Kanhaiya
Guide(s): Singh Kiran
Keywords: healing
Heat shock proteins (HSPs)
Life Sciences
Matrix metalloproteinases
myeloid cells
University: Banaras Hindu University
Completed Date: 2015
Abstract: Wound healing cascade comprise of a series of mutually dependent phases like homeostasis, inflammation, proliferation and remodeling. Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycaemia which bring about a chain of abrupt biochemical and physiological changes. Through the present work an attempt has been made to associate genetic and epigenetic alterations in the candidate genes involved in the regulation of different phases of wound healing. Compromised immune regulation is the hall mark of T2DM and may also contribute to impaired wound healing process. During the inflammatory phase of wound healing, innate immune system activation is crucial to combat invading microbes. Toll like receptors (TLRs) are the important members of innate immune system which act against pathogens through a series of downstream signalling molecules. Recently, TLRs have been shown to be an important regulator of wound repair and regeneration in mouse model. We observed differential expression of extracellular (TLR2 and TLR4) in human diabetic wounds. Epigenetic silencing mediated by methylation analysis of CpGs of promoter regions of TLR2 and TLR4 revealed that this mechanism is contributing towards the down-regulation of TLR2 and TLR4. Some endosomal TLRs like TLR7 and TLR9 have been shown to promote tissue necrosis and sensory neuropathy. The levels of these endosomal TLRs were found to be significantly elevated in diabetic wounds along with their signalling molecules like S100A8 and IL8. Recruitment of anti-inflammatory CD11b+ CD33+ myeloid cells during initial phase of wound healing is necessary for proper healing. Comparative analysis of the counts of these CD11b+ CD33+ myeloid cells using flow cytometry in healthy controls, T2DM cases and Diabetic foot ulcer (DFU) cases revealed the reduced level of these cells to be involved in the impairment of wound healing.
Appears in Departments:Department of Molecular & Human Genetics

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