Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Key Laboratory of Proteomics of Chongqing, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing, China.
Department of Plastic and Reconstructive Surgery, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing, China.
J Cell Mol Med. 2021 Feb;25(4):1939-1948. doi: 10.1111/jcmm.15925. Epub 2020 Dec 27.
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.
表皮干细胞（EpSCs）的迁移对于伤口再上皮化和伤口愈合至关重要。最近，发现生长/分化因子-5（GDF-5）对伤口愈合具有多种生物学作用；然而，其在 EpSCs 中的作用尚不清楚。在这项工作中，通过体外活体成像发现重组小鼠 GDF-5（rmGDF-5）促进了伤口划痕模型中小鼠 EpSCs 的迁移。Western blot 和实时 PCR 检测表明 RhoA 和基质金属蛋白酶-9（MMP9）的表达水平与 rmGDF-5 浓度相关。此外，我们发现 rmGDF-5 通过 RhoA 信号通路调节 MMP9 的表达，在 mRNA 和蛋白质水平上刺激小鼠 EpSC 的迁移。此外，在体内深Ⅱ度烫伤小鼠模型中，通过 BrdU 标记细胞的追踪证实 GDF-5 通过 RhoA 促进 EpSC 迁移和 MMP9 表达。本研究表明 rmGDF-5 可促进小鼠 EpSC 的体外和体内迁移，GDF-5 可通过 RhoA-MMP9 信号触发 EpSCs 的迁移。
