Determination of Novel Strategies for Hastening Corneal Wound Healing and Reducing Tissue Inflammation

摘要

The aim of this study is to uncover novel transient receptor potential protein vanilloid-1 (TRPV1)- linked cell signaling drug targets for more selective alleviation of trauma-induced corneal symptomology and faster restoration of normal vision. Dual specificity phosphatase (DUSP)5 and DUSP6 selectively control ERK pathway activity and proliferation in human corneal epithelial cells (HCEC). Capsaicin-induced increases in interleukin (IL)-6 and IL-8 occur primarily through phosphorylated JNK1. CB1 and TRPV1 activation induces increases in HCEC proliferation and migration through epidermal growth factor receptor (EGFR) transactivation leading to global mitogen activated protein kinase (MAPK) pathway stimulation. On the other hand, the TRPV1- mediated increases in IL-6 and IL-8 release are elicited through both EGF- dependent and EGFR-independent signaling pathways. Drug-induced modulation of transforming growth factor kinase 1 (TAK-1) activation is a potential target to selectively suppress dysregulated inflammation without compromising TRPV1 promotion of wound healing. In vivo studies demonstrated that TRPV1 activation accelerates epithelial wound healing response in a mice epithelial debridement wound healing model through stimulation of cell proliferation.