激活素 B 激活的 Cdc42 信号通路在调节脂肪来源的间充质干细胞介导的皮肤伤口愈合中发挥关键作用。

Activin B-activated Cdc42 signaling plays a key role in regulating adipose-derived mesenchymal stem cells-mediated skin wound healing.

机构信息

Department of Histology and Embryology, NMPA Key Laboratory for Safety Evaluation of Cosmetics, Key Laboratory of Construction and Detection in Tissue Engineering of Guangdong Province, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Department of Orthopedics, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics Guangdong Province, Guangzhou, 510630, Guangdong, China.

出版信息

Stem Cell Res Ther. 2022 Jun 11;13(1):248. doi: 10.1186/s13287-022-02918-9.

DOI:10.1186/s13287-022-02918-9

PMID:35690801

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9188063/

Abstract

BACKGROUND

In our previous study, activin B in combination with ADSCs enhances skin wound healing. However, the underlying molecular mechanisms are not well studied. Cdc42 is recognized to play a critical role in the regulation of stem cells.

METHODS

Pull-down assay was performed to investigate the activity of Cdc42. The dominant-negative mutant of Cdc42 (Cdc42N17) was used to explore the role of Cdc42 in activin B-induced ADSCs migration, proliferation, and secretion in vitro. Cdc42N17-transfected ADSCs were injected into a full-thickness excisional wound model to explore their efficiency in wound healing in vivo. The wound healing efficacy was evaluated by the wound closure rates and histological examination. The neovascularization and wound contraction were detected by immunohistochemistry staining of CD31 and α-SMA. Finally, the underlying mechanisms were explored by RNA sequencing.

RESULTS

Cdc42N17 inhibited ADSCs migration, proliferation, and secretion induced by activin B. Furthermore, Cdc42N17-transfected ADSCs inhibited the wound closure rate and suppressed the expression of CD31 and α-SMA induced by activin B in vivo. The RNA sequencing showed that the differentially expressed genes in Cdc42N17-transfected ADSCs versus ADSCs were associated with cell migration, proliferation, and adhesion. Further study revealed that the Cdc42-Erk-Srf pathway was required for activin B-induced proliferation in ADSCs.

CONCLUSIONS

Our study indicates that Cdc42 plays a crucial role in ADSCs-mediated skin wound healing induced by activin B.

摘要

背景

在我们之前的研究中，激活素 B 与 ADSCs 联合使用可增强皮肤伤口愈合。然而，其潜在的分子机制尚未得到充分研究。Cdc42 被认为在干细胞的调控中发挥关键作用。

方法

采用下拉实验检测 Cdc42 的活性。使用 Cdc42 的显性失活突变体（Cdc42N17）来探索 Cdc42 在激活素 B 诱导的 ADSCs 迁移、增殖和分泌中的作用。将 Cdc42N17 转染的 ADSCs 注射到全层切除创面模型中，以探索其在体内促进伤口愈合的效果。通过创面闭合率和组织学检查评估创面愈合效果。通过 CD31 和 α-SMA 的免疫组化染色检测新生血管形成和创面收缩。最后，通过 RNA 测序探索潜在机制。

结果

Cdc42N17 抑制激活素 B 诱导的 ADSCs 迁移、增殖和分泌。此外，Cdc42N17 转染的 ADSCs 抑制了激活素 B 体内诱导的创面闭合率，并抑制了 CD31 和 α-SMA 的表达。RNA 测序显示，Cdc42N17 转染的 ADSCs 与 ADSCs 之间差异表达的基因与细胞迁移、增殖和黏附有关。进一步的研究表明，Cdc42-Erk-Srf 通路是激活素 B 诱导 ADSCs 增殖所必需的。