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Extracellular vesicles bearing vimentin drive epithelial-mesenchymal transition
Tekijät: Parvanian, Sepideh; Coelho-Rato, Leila S.; Silva Santos, Michael; Sultana, Giulia; Venu, Arun P.; Devre, Pallavi Vilas; Modi, Mayank Kumar; Eriksson, John E.
Kustantaja: Elsevier Inc.
Julkaisuvuosi: 2025
Lehti: Molecular and Cellular Proteomics
Artikkelin numero: 101028
Vuosikerta: 24
Numero: 12
ISSN: 1535-9476
eISSN: 1535-9484
DOI: https://doi.org/10.1016/j.mcpro.2025.101028
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Kokonaan avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1016/j.mcpro.2025.101028
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/500037319
Epithelial-mesenchymal transition (EMT) is a key biological process in physiological and pathological conditions, spanning development, wound healing, and cancer. Vimentin, a key cytoskeletal intermediate filament (IF) protein, is an established intracellular determinant of EMT. Recently, extracellular vimentin has also emerged with important functions, and we demonstrated that vimentin from fibroblast-derived extracellular vesicles (EVs) promotes wound healing. Building on these findings, we explored whether extracellular vimentin regulates EMT.We employed fibroblast-derived EVs to assess their EMT-driving capacity. Using co-culture models and EV treatments from wild-type and vimentin-knockout fibroblasts, we observed that fibroblasts induce an EMT phenotype in epithelial cells, marked by elevated mesenchymal markers and reduced epithelial markers. EVs from vimentin-deficient fibroblasts showed a decreased EMT-inducing capacity and failed to stimulate cell cover closure, underscoring vimentin’s critical role in orchestrating these processes. Co-culturing epithelial cells with wild-type fibroblasts mirrored these outcomes, while vimentin-deficient fibroblasts produced similarly poor EMT induction.Proteomic profiling revealed that wild-type EVs contained an enriched set of EMT-associated proteins, including those involved in cytoskeletal organization, cell adhesion, and EMT-regulating signaling pathways. Notably, these proteins, such as fibronectin and N-cadherin, were significantly diminished in vimentin-deficient EVs. Moreover, we identified over 600 additional proteins uniquely present in WT-derived EVs, with enrichment in key biological processes like wound healing and cell migration.These findings demonstrate that vimentin-positive EVs drive EMT by transmitting a specific protein cargo that supports EMT-related cellular changes. The vimentin-positive EV proteome will help understand EMT mechanisms and develop targeted therapies for pathological conditions related to abnormal EMT.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
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This work was supported by Academy of Finland, Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, Magnus Ehrnrooth Foundation, K. Albin Johanssons stiftelse, Otto A Malm Foundation, Finnish Cultural Foundation, Swedish Cultural Foundation, Ella and Georg Ehrnrooth Foundation, Emil Altonen, Maud Kuistila and Instrumentarium. The proteomics study was done at the Proteomics Core Facility, and imaging at the Imaging Core Facility of Turku Bioscience was supported by Biocenter Finland. TEM and NTA analyses were performed by the EV Core at the University of Helsinki. Vim-/-HDFs were obtained in collaboration with the Genome Editing Core, Turku Bioscience Centre.
