Impairment Of Diabetic Wound Healing: Key Genetic Players | 38996
Journal of Biotechnology & Biomaterials
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Type-2 Diabetes Mellitus (T2DM) is a multifactorial disease characterized by hyperglycaemia and a series of micro- and
macro-vascular secondary complications including wound healing impairment. Acute inflammation is necessary for
wound healing as it brings about proper wound debridement. 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 and are shown to be an important regulator of wound repair and regeneration in mouse model. We
observed differential expression of extracellular TLRs 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 downregulation
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. In conclusion, our study indicated that the combined genetic
and epigenetic deregulation of immuno-inflammatory phase due to persistent hyperglycaemia lead to development of chronic
ulcers in T2DM subjects.
Kiran Singh has completed her PhD from Cytogenetics Laboratory, Department of Zoology; Banaras Hindu University in 2005. She is currently working as an Assistant Professor in Department of Molecular and Human Genetics, Banaras Hindu University. Her area of interest includes molecular human reproductive genetics, clinical cytogenetics & genetics and epigenetics of diabetic wound healing impairment. She has published 48 papers in various national and international journals and has been serving as Reviewer and Editorial Board Member of various reputed journals.