MED1 Ablation Promotes Oral Mucosal Wound Healing via JNK Signaling Pathway

Abstract

Mediator complex subunit 1 (MED1) is a coactivator of multiple transcription factors and plays a key role in regulating epidermal homeostasis as well as skin wound healing. It is unknown, however, whether it plays a role in healing oral mucosal wounds. In this study, we investigate MED1’s functional effects on oral mucosal wound healing and its underlying mechanism. The epithelial-specific MED1 null (Med1epi−/−) mice were established using the Cre-loxP system with C57/BL6 background. A 3 mm diameter wound was made in the cheek mucosa of the 8-week-old mice. In vivo experiments were conducted using HE staining and immunostaining with Ki67 and uPAR antibodies. The in vitro study used lentiviral transduction, scratch assays, qRT-PCR, and Western blotting to reveal the underlying mechanisms. The results showed that ablation of MED1 accelerated oral mucosal wound healing in 8-week-old mice. As a result of ablation of MED1, Activin A/Follistatin expression was altered, resulting in an activation of the JNK/c-Jun pathway. Similarly, knockdown of MED1 enhanced the proliferation and migration of keratinocytes in vitro, promoting re-epithelialization, which accelerates the healing of oral mucosal wounds. Our study reveals a novel role for MED1 in oral keratinocytes, providing a new molecular therapeutic target for accelerated wound healing.