Department of Nutrition and Food Technology, Health Sciences PhD Program, Universidad Católica de Murcia (UCAM), Campus de los Jerónimos nº135, Guadalupe, 30107, Murcia, Spain.
Regeneration, Molecular Oncology and TGF-ß, Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
Sci Rep. 2022 Sep 5;12(1):15065. doi: 10.1038/s41598-022-17553-w.
Cell migration is a critical process for wound healing, a physiological phenomenon needed for proper skin restoration after injury. Wound healing can be compromised under pathological conditions. Natural bioactive terpenoids have shown promising therapeutic properties in wound healing. Oleanolic acid (OA), a triterpenoid, enhances in vitro and in vivo cell migration. However, the underlying signaling mechanisms and pathways triggered by OA are poorly understood. We have previously shown that OA activates epidermal growth factor receptor (EGFR) and downstream effectors such as mitogen-activated protein (MAP) kinase cascade and c-Jun N-terminal kinase (JNK), leading to c-Jun transcription factor phosphorylation, all of which are involved in migration. We performed protein expression or migration front protein subcellular localization assays, which showed that OA induces c-Jun activation and its nuclear translocation, which precisely overlaps at wound-edge cells. Furthermore, c-Jun phosphorylation was independent of EGFR activation. Additionally, OA promoted actin cytoskeleton and focal adhesion (FA) dynamization. In fact, OA induced the recruitment of regulator proteins to FAs to dynamize these structures during migration. Moreover, OA changed paxillin distribution and activated focal adhesion kinase (FAK) at focal adhesions (FAs). The molecular implications of these observations are discussed.
细胞迁移是伤口愈合的关键过程，是受伤后皮肤正常恢复所必需的生理现象。在病理条件下，伤口愈合可能会受到影响。天然生物活性萜类化合物在伤口愈合方面显示出有希望的治疗特性。齐墩果酸 (OA) 是一种三萜，可增强体外和体内细胞迁移。然而，OA 触发的潜在信号机制和途径知之甚少。我们之前曾表明，OA 激活表皮生长因子受体 (EGFR) 和下游效应子，如丝裂原活化蛋白 (MAP) 激酶级联和 c-Jun N 端激酶 (JNK)，导致 c-Jun 转录因子磷酸化，所有这些都参与迁移。我们进行了蛋白质表达或迁移前沿蛋白质亚细胞定位测定，结果表明 OA 诱导 c-Jun 激活及其核易位，这与伤口边缘细胞完全重叠。此外，c-Jun 磷酸化与 EGFR 激活无关。此外，OA 促进肌动蛋白细胞骨架和黏着斑 (FA) 动力学。事实上，OA 诱导调节蛋白募集到 FA 以在迁移过程中动态化这些结构。此外，OA 改变了粘着斑 (FA) 中的桩蛋白分布并激活粘着斑激酶 (FAK)。讨论了这些观察结果的分子意义。
