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.

Phosphoproteomic analysis reveals the role of A-Raf in regulating the apoptosis of porcine macrophages infected with Toxoplasma gondii

“…CDK7 could directly phosphorylates Med1 at T1457 to in uence castration-resistant prostate cancer [49]. Med1 has also been shown to regulate the Jun amino-terminal kinase (JNK) /c-Jun pathway [50]. In this study, Med1 was phosphorylated at S1418 after T. gondii infection and dephosphorylated after A-Raf knockout in 3D4/21 cells.…”

Topical metformin accelerates wound healing by promoting collagen synthesis and inhibiting apoptosis in a diabetic wound model

“… 9 Evidence from recent in vitro wound model studies have shown that c‐Jun expression increases as a result of treatment with different agents, which promotes the migration and proliferation of keratinocytes, thereby accelerating wound healing. 40 , 41 , 42 However, in another study, they showed that high glucose increased the mRNA and protein level of AP1 subunits c‐Fos/c‐Jun, resulting in the activation of AP1 in diabetic skin tissue. 43 In an in vivo wound model, photobiomodulation treatment combined with a topical hydrogel prepared from the fruit of Lycium barbarum was shown to decrease MMP‐1/‐2/‐9 expression as well as c‐Fos/c‐Jun, and increase collagen I/III level, inhibit skin thickening caused by ultraviolet radiation.…”

“…In addition, phosphorylated AP‐1 is also known to regulate genes involved in wound healing, such as growth factors and MMPs 9 . Evidence from recent in vitro wound model studies have shown that c‐Jun expression increases as a result of treatment with different agents, which promotes the migration and proliferation of keratinocytes, thereby accelerating wound healing 40–42 . However, in another study, they showed that high glucose increased the mRNA and protein level of AP1 subunits c‐Fos/c‐Jun, resulting in the activation of AP1 in diabetic skin tissue 43 .…”

Recombination humanized type III collagen promotes oral ulcer healing

“…Cell migration was monitored and photographed after 12, 24, and 36 h, respectively. The relative migration rate was calculated as (original scratch area‐point scratch area)/original scratch area × 100% (Meng et al, 2022).…”