RNAi-based Gene Therapy Targeting ZGPAT Promotes EGF-dependent Wound Healing

Abstract

Wound-healing is a multi-dynamic skin repair process that involves a sequence of events, such as inflammation, proliferation, and migration of different cell types like fibroblasts. Epidermal growth factor (EGF) is an excellent wound healing agent, and epidermal growth factor receptor (EGFR) becomes particularly important for wound healing. Zinc Finger CCCH-type with G-Patch Domain Containing Protein (ZGPAT), encodes a protein that has its main role as a transcription repressor by binding to a specific DNA sequence and is capable of inhibiting the expression of EGFR. We hypothesize that targeting ZGPAT with RNA-interference-based gene therapy will improve wound healing by alleviating inhibition of EGFR expression. We used EGF and siRNA to inhibit ZGPAT in a normal skin cell line, Detroit 551 with migration assay as a model for wound healing. The aim of the study was to find out whether inhibiting ZGPAT will expedite the wound healing process by accelerating cell migration. We found that downregulation of ZGPAT by siRNA increased EGFR expression in Detroit 551. Further, simultaneous treatment of siZGPAT and EGF significantly increased cell migration in Detroit 551 cells. This novel combination of treatment can provide a key to the development of wound healing strategies in medicine and cellular biology.