Epidermal Growth Factor based Therapy Promotes Intracellular Trafficking and Accumulation of its Receptor in the Nucleus of Fibroblasts from Diabetic Foot Ulcers
| Autor: | Ricardo Bringas-Pérez, Mariuska Matos-Terrero, Ivón Menéndez-Valdés, Ivonne Salgado, Yssel Mendoza-Marí, Rocío Garateix-Suárez, Sirenia González-Pozos, ro Hernández-Seara, David G. Armstrong, Lilianne López-Noudo, Jorge Berlanga-Acosta, Maday Fernández-Mayola, Karla Pereira-Yañez, Ariana García-Ojalvo, Nelson Acosta-Rivero, Maritza González, Juan Kourí-Flores, Viviana Falcón-Cama, Alej, William Savigne-Gutierrez |
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| Rok vydání: | 2016 |
| Předmět: |
Pathology
medicine.medical_specialty biology business.industry media_common.quotation_subject Immunoelectron microscopy Granulation tissue medicine.disease Proliferating cell nuclear antigen Immunolabeling medicine.anatomical_structure Epidermal growth factor biology.protein Cancer research Medicine Internalization business Receptor Infiltration (medical) hormones hormone substitutes and hormone antagonists media_common |
| Zdroj: | Journal of Diabetic Complications & Medicine. |
| ISSN: | 2475-3211 |
| Popis: | Objective: To gain a better understanding of the Epidermal Growth Factor (EGF) Receptor (EGFR) activation, trafficking and biological response in diabetic foot ulcers (DFU), exposed to recombinant human EGF via intra-ulcer infiltration as a healing alternative. Methods: We studied by immunoelectron microscopy the intracellular localization of the EGFR and Proliferating Cell Nuclear Antigen (PCNA) in fibroblast-like cells (FLC) from granulation tissue of DFU patients, collected before and at different time points after EGF treatment. Results: EGF therapy appears to increase EGFR immunolabeling. At early time-points, EGFR labeling is observed predominantly in the nucleus, suggesting a fast EGFR internalization and nuclear translocation. Interestingly EGFR is also detected in the mitochondrial outer membrane. PCNA expression and trafficking were also detected in a time-dependent manner after EGF infiltration. Conclusion: Differential subcellular distribution of EGFR and PCNA and accumulation in the nucleus, in a timepoint specific manner, supports the induction of an EGF-mediated activation program that is sustained for at least 24 hours after the EGF administration. These findings substantiate the therapeutic ability of EGF to restore the healing process in DFU. |
| Databáze: | OpenAIRE |
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