RIG‐I contributes to keratinocyte proliferation and wound repair by inducing TIMP‐1 expression through NF‐κB signaling pathway

Abstract

AbstractEpithelial keratinocyte proliferation is an essential element of wound repair, and chronic wound conditions, such as diabetic foot, are characterized by aberrant re‐epithelialization. In this study, we examined the functional role of retinoic acid inducible‐gene I (RIG‐I), a key regulator of epidermal keratinocyte proliferation, in promoting TIMP‐1 expression. We found that RIG‐I is overexpressed in keratinocytes of skin injury and underexpressed in skin wound sites of diabetic foot and streptozotocin‐induced diabetic mice. Moreover, mice lacking RIG‐I developed an aggravated phenotype when subjected to skin injury. Mechanistically, RIG‐I promoted keratinocyte proliferation and wound repair by inducing TIMP‐1 via the NF‐κB signaling pathway. Indeed, recombinant TIMP‐1 directly accelerated HaCaT cell proliferation in vitro and promoted wound healing in Ddx58−/− and diabetic mice in vivo. In summary, we demonstrated that RIG‐I is a crucial factor that mediates epidermal keratinocyte proliferation and may be a potential biomarker for skin injury severity, thus making it an attractive locally therapeutic target for the treatment of chronic wounds such as diabetic foot.