Deregulation of epigenetic factor, KDM6A, is involved during Candida albicans mediated delayed wound healing

Abstract

Deregulation of wound healing process leads to chronic non-healing wounds. Opportunistic fungal pathogens like Candida albicans is known to colonize open wounds leading to delayed, insufficient, or disorganized healing. In our study, we investigate the regulatory mechanisms orchestrating this C. albicans mediated delay of wound healing and underscore a critical role for the transcription factor c-AMP Response Element Binding Protein (CREB) in regulating pro-inflammatory cytokines and genes implicated in wound healing. Parallelly, we found the epigenetic factor, KDM6A (Ubiquitously Transcribed tetratricopeptide repeat on chromosome X, also known as UTX) to be downregulated upon infection and modulating expression of metalloproteinases during C. albicans governed wound healing impairment. Mechanistically, we observed enhanced recruitment of EZH2, a methyl transferase, over the promoters of KDM6A during infection, hence, governing its expression. Our findings, therefore, underscore a role of KDM6A and CREB in C. albicans mediated delayed wound healing.