Oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism
Abstract 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. Olea...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17553-w |
| _version_ | 1811273800260517888 |
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| author | Javier Stelling-Férez José Antonio Gabaldón Francisco José Nicolás |
| author_facet | Javier Stelling-Férez José Antonio Gabaldón Francisco José Nicolás |
| author_sort | Javier Stelling-Férez |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T23:05:50Z |
| format | Article |
| id | doaj.art-89fe1ad6043c40e7b8f6b7532ecbb62c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T23:05:50Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-89fe1ad6043c40e7b8f6b7532ecbb62c2022-12-22T03:12:55ZengNature PortfolioScientific Reports2045-23222022-09-0112111610.1038/s41598-022-17553-wOleanolic acid stimulation of cell migration involves a biphasic signaling mechanismJavier Stelling-Férez0José Antonio Gabaldón1Francisco José Nicolás2Department of Nutrition and Food Technology, Health Sciences PhD Program, Universidad Católica de Murcia (UCAM)Department of Nutrition and Food Technology, Health Sciences PhD Program, Universidad Católica de Murcia (UCAM)Regeneration, Molecular Oncology and TGF-ß, Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Hospital Clínico Universitario Virgen de la ArrixacaAbstract 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.https://doi.org/10.1038/s41598-022-17553-w |
| spellingShingle | Javier Stelling-Férez José Antonio Gabaldón Francisco José Nicolás Oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism Scientific Reports |
| title | Oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism |
| title_full | Oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism |
| title_fullStr | Oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism |
| title_full_unstemmed | Oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism |
| title_short | Oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism |
| title_sort | oleanolic acid stimulation of cell migration involves a biphasic signaling mechanism |
| url | https://doi.org/10.1038/s41598-022-17553-w |
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