Activin B Promotes BMSC-Mediated Cutaneous Wound Healing by Regulating Cell Migration via the JNK—ERK Signaling Pathway

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) are able to differentiate into various types of skin cells and participate in skin regeneration and repair. Activin signaling can regulate wound healing and reepithelialization. The present study assessed the impact of activin B on BMSC-mediated cutaneous wound healing in rats and explored the possible mechanism involved. We found that CFSE-labeled BMSCs participated in wound healing in vivo, and compared to administration with PBS, activin B, or BMSCs, activin B plus BMSCs significantly promoted wound healing and hair follicle regeneration. Activin B induced actin stress fiber formation and cell migration in BMSCs in vitro. Activation of JNK and ERK, but not p38, was required for activin B-induced actin stress fiber formation and BMSC migration. These results show that activin B may promote BMSC-mediated wound healing by inducing actin stress fiber formation and BMSC migration via the ERK and JNK signal pathways. Combined administration of BMSCs and cytokines may be a promising therapeutic strategy for the management of skin wounds.

Overexpression of activin-A and -B in malignant mesothelioma – Attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth

“…These include the ERK and JNK MAP kinase pathways, which have been shown to contribute to cell migration [17,20]. ERK phosphorylation, i.e., activation was analyzed by Western blotting after treatment of cells with activin-A or -B for 90 min.…”

“…Activin-A can induce ERK and p38 MAP kinase phosphorylation [17], and activin-B has been reported to be able to phosphorylate SAPK/JNK and to induce keratinocyte migration [18] and wound healing [19]. Furthermore, activation of both JNK and ERK is required for activin-B induced migration in bone marrow-derived mesenchymal stem cells [20]. Activin-A and activin-B have partially overlapping expression patterns but are functionally distinct [21].…”

P75 neurotrophin receptor activates epidermal stem cell differentiation via ERK, JNK and AKT pathways

“…Mechanically, ERK signalling pathway plays an important role in regulating the migration of epithelial cells during wound healing [20][21][22]. When ERK was activated, ERK translocated into the nucleus to regulate cellular proliferation [23,24].…”

A drug delivery hydrogel system based on activin B for Parkinson's disease

“…In our previous work, it was proved that activin B can promote the migration of Bone marrow-derived mesenchymal stem cells (BMSCs) to the scratch wound [46], on this basis, we chose BMSCs to perform wound healing assay following our established Assays were performed in quadruplicate.…”

“…The activity of activin B released from hydrogel was further characterized using the previously established BMSC migration bioassay [46]. When bioactive activin B is added to the culture, the migration of BM-MSCs to the scratch wound was promoted.…”