Zhang Lei, Xu Pengcheng, Wang Xueer, Zhang Min, Yan Yuan, Chen Yinghua, Zhang Lu, Zhang Lin
Key Laboratory of Construction and Detection in Tissue Engineering of Guangdong Province, Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Int J Biochem Cell Biol. 2017 Jun;87:69-76. doi: 10.1016/j.biocel.2017.04.004. Epub 2017 Apr 8.
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.
脂肪来源干细胞（ADSCs）是多能基质细胞，能够分化为多种细胞类型，包括皮肤细胞，并且它们可为皮肤组织工程和皮肤伤口愈合提供丰富的细胞来源。本研究的目的是探讨激活素B与ADSCs联合应用的治疗效果及其可能的信号传导机制。在本研究中，我们发现激活素B在体外能够通过诱导肌动蛋白应力纤维形成来促进ADSCs迁移。在体内，激活素B与ADSCs联合应用能够增强α-SMA表达并促进伤口闭合。这种联合治疗还能促进成纤维细胞和角质形成细胞增殖，加速再上皮化和胶原蛋白沉积。此外，激活素B与ADSCs联合应用能促进伤口区域的血管生成。对机制的进一步研究表明，激活素B诱导ADSCs肌动蛋白应力纤维形成和细胞迁移需要JNK和ERK信号通路的激活，而不是p38信号通路。这些结果表明，激活素B能够激活JNK和ERK信号通路，诱导肌动蛋白应力纤维形成和ADSCs迁移，从而促进伤口愈合。这些结果提示，激活素B与ADSCs联合治疗是一种治疗严重皮肤伤口的有前景的治疗策略。
