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

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

  • Stem Cell Res Ther. 2022 Jun 11;13(1):248. doi: 10.1186/s13287-022-02918-9.
Simin Huang  # 1,  Xueer Wang  # 1,  Min Zhang 1,  Mianbo Huang 1,  Yuan Yan 1,  Yinghua Chen 1,  Yijia Zhang 1,  Jinfu Xu 1,  Lingwei Bu 1,  Ruyi Fan 1,  Huiyi Tang 1,  Canjun Zeng 2,  Lu Zhang 3,  Lin Zhang 4
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Orthopedics, Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics Guangdong Province, Guangzhou, 510630, Guangdong, China.
  • 3 Key Laboratory of Functional Proteomics of Guangdong Province, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • 4 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. [email protected].
  • # Contributed equally.
PMID: 35690801 DOI: 10.1186/s13287-022-02918-9
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.

Keywords

ADSCs; Cdc42; RNA-seq; Wound healing.

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