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Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption
Published on: October 4, 2019
がん患者の創傷治癒を促進するコネキシン43を標的としたナノカプセル化された治療薬化合物
Marina Rodríguez-Candela Mateos1, Jenifer García-Fernández2, Sofia M Saraiva2
1Institute of Biomedical Research of A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, A Coruña 15006, Spain.
Abstract:
Oncological patients receiving radiotherapy or chemotherapy often experience impaired wound healing due to tissue damage and cellular senescence. Connexin43 (Cx43) is a key regulator in this process, promoting senescence and the SASP, which hinder regeneration. This study investigates targeting Cx43 in primary dermal fibroblasts from cancer patients using a new combination of nanoencapsulated drugs. We show that Cx43 overexpression correlates with reduced gap junction communication, increased senescence, and delayed healing. Treatment with oleuropein (OLP), a polyphenol with antioxidant and regenerative properties, restores fibroblast function, reduces senescence, and improves healing. We also examine the p38 MAPK inhibitor BIRB796, alone and with OLP, demonstrating its ability to suppress SASP and support tissue repair. After confirming the superior combined effect of OLP and BIRB796, we developed a co-encapsulated nanoformulation. This innovative approach may significantly enhance wound healing in oncological patients.

