Activin B regulates adipose-derived mesenchymal stem cells to promote skin wound healing via activation of the MAPK signaling pathway

• DOI: 10.1016/j.biocel.2017.04.004
• Publication Date: 2017-04-08T04:17:01Z
• Authors: Lei Zhang; Pengcheng Xu; Xueer Wang; Min Zhang; Yuan Yan; Yinghua Chen; Lu Zhang; Lin Zhang
• Keywords: Keratinocytes; 0301 basic medicine; MAP Kinase Signaling System; JNK Mitogen-Activated Protein Kinases; Neovascularization, Physiologic; Mesenchymal Stem Cells; Fibroblasts; Actins; Activins; 3. Good health; Enzyme Activation; Mice; 03 medical and health sciences; Adipose Tissue; Cell Movement; Stress Fibers; Animals; Female; Collagen; Phosphorylation; Extracellular Signal-Regulated MAP Kinases; Cell Proliferation; Skin

Adipose-derived stem cells (ADSCs) are multipotent stromal cells that can differentiate into a variety of cell types, including skin cells, and they can provide an abundant source of cells for skin tissue engineering and skin wound healing. The purpose of this study is to explore the therapeutic effects of activin B in combination with ADSCs and the possible signaling mechanism. In this study, we found that activin B was able to promote ADSC migration by inducing actin stress fiber formation in vitro. In vivo, activin B in combination with ADSCs was capable of enhancing α-SMA expression and wound closure. This combined treatment also promoted fibroblast and keratinocyte proliferation and accelerated re-epithelialization and collagen deposition. Moreover, activin B in combination with ADSCs boosted angiogenesis in the wound area. Further study of the mechanism revealed that activation of JNK and ERK signaling, but not p38 signaling, were required for activin B-induced ADSC actin stress fiber formation and cell migration. These results showed that activin B was able to activate JNK and ERK signaling pathways to induce actin stress fiber formation and ADSC migration to promote wound healing. These results suggest that combined treatment with activin B and ADSCs is a promising therapeutic strategy for the management of serious skin wounds.