GDF‐5 induces epidermal stem cell migration via RhoA‐MMP9 signalling

• Published in: Journal of cellular and molecular medicine Vol. 25; no. 4; pp. 1939 - 1948
• Main Authors: Li, Xue, Wang, Fan, Lan, Yuanxin, Bian, Ruyu, Wang, Ying, Zhang, Xiaorong, Guo, Yicheng, Xiao, Ling, Ni, Wenqiang, Zhao, Xiaohong, Luo, Gaoxing, Zhan, Rixing
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2021; John Wiley and Sons Inc
• Subjects: Antibodies; Cartilage; Cell adhesion & migration; Cell growth; Cell migration; Collagen; Epidermal growth factor; epidermal stem cells; Flow cytometry; Gelatinase B; Gene expression; growth/differentiation factor‐5; Homeostasis; Kinases; Matrix metalloproteinase; matrix metalloproteinases; Medical research; Metalloproteinase; Motility; mRNA; Original; Proteins; RhoA protein; Scald; Signal transduction; Stem cell transplantation; Stem cells; Wound healing; cell migration; epidermal stem cells; growth/differentiation factor-5; matrix metalloproteinases
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15925

The migration of epidermal stem cells (EpSCs) is critical for wound re‐epithelization and wound healing. Recently, growth/differentiation factor‐5 (GDF‐5) was discovered to have multiple biological effects on wound healing; however, its role in EpSCs remains unclear. In this work, recombinant mouse GDF‐5 (rmGDF‐5) was found via live imaging in vitro to facilitate the migration of mouse EpSCs in a wound‐scratch model. Western blot and real‐time PCR assays demonstrated that the expression levels of RhoA and matrix metalloproteinase‐9 (MMP9) were correlated with rmGDF‐5 concentration. Furthermore, we found that rmGDF‐5 stimulated mouse EpSC migration in vitro by regulating MMP9 expression at the mRNA and protein levels through the RhoA signalling pathway. Moreover, in a deep partial‐thickness scald mouse model in vivo, GDF‐5 was confirmed to promote EpSC migration and MMP9 expression via RhoA, as evidenced by the tracking of cells labelled with 5‐bromo‐2‐deoxyuridine (BrdU). The current study showed that rmGDF‐5 can promote mouse EpSC migration in vitro and in vivo and that GDF‐5 can trigger the migration of EpSCs via RhoA‐MMP9 signalling.