Abstract
During wound healing, skin function is restored by the action of several cell types that undergo differentiation, migration, proliferation and/or apoptosis. These dynamics are tightly regulated by the evolution of the extra cellular matrix (ECM) contents along the process. Pharmacologically active flavonoids have shown to exhibit useful physiological properties interesting in pathological states. Among them, oleanolic acid (OA), a pentacyclic triterpene, shows promising properties over wound healing, as increased cell migration in vitro and improved wound resolution in vivo. In this paper, we pursued to disclose the molecular mechanisms underlying those effects, by using an in vitro scratch assay in two epithelial cell lines of different linage: non-malignant mink lung epithelial cells, Mv1Lu; and human breast cancer cells, MDA-MB-231. In every case, we observed that OA clearly enhanced cell migration for in vitro scratch closure. This correlated with the stimulation of molecular pathways related to mitogen-activated protein (MAP) kinases, as ERK1,2 and Jun N-terminal kinase (JNK) 1,2 activation and c-Jun phosphorylation. Moreover, MDA-MB-231 cells treated with OA displayed an altered gene expression profile affecting transcription factor genes (c-JUN) as well as proteins involved in migration and ECM dynamics (PAI1), in line with the development of an epithelial to mesenchymal transition (EMT) status. Strikingly, upon OA treatment, we observed changes in the epidermal growth factor receptor (EGFR) subcellular localization, while interfering with its signalling completely prevented migration effects. This data provides a physiological framework supporting the notion that lipophilic plant extracts used in traditional medicine, might modulate wound healing processes in vivo through its OA contents. The molecular implications of these observations are discussed.
Highlights
During wound healing, skin function is restored by the action of numerous cell types
Non-malignant mink lung epithelial cells Mv1Lu, which are recognized as a good model for cell migration studies [15,16,17], were used in wound healing scratch experiments to assess oleanolic acid (OA) properties
Cells exposed to OA in combination with MEK inhibitor PD98059 (MEKi) plus JNK inhibitor SP600125 (JNKi) achieved similar migratory performance than cells exposed to EGFR inhibitor PD153035 (EGFRi) or EGFRi and OA (Fig 2B). Everything included, these results strongly suggest that OA induces cell migration with the involvement of active MEK and Jun N-terminal kinase (JNK) kinases signalling under the influence of the epidermal growth factor receptor (EGFR) activities
Summary
Skin function is restored by the action of numerous cell types. These cells undergo proliferation, differentiation, migration, and apoptosis [1]. The instantaneous response triggers a cascade of events that ends in the formation of a three-dimensional structure, the fibrin clot, that halts bleeding and will serve as provisional matrix for the migration of inflammatory and structural cells to the wound site [2]. IL-1, EGF, or TGF-ß, are known to play important roles [1]. These factors are released by a variety of cells (e.g., platelets, neutrophils, fibroblasts, endothelial cells, macrophages, and lymphocytes) and they accumulate within the provisional matrix and ECM [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
