Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds
| Autor: | Hannah M Thomas, Allison J. Cowin, Xanthe L. Strudwick, Parinaz Ahangar, Robert Fitridge, Stuart J. Mills, Benjamin R Hofma |
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| Přispěvatelé: | Thomas, Hannah M, Ahangar, Parinaz, Hofma, Benjamin R, Strudwick, Xanthe L, Fitridge, Robert, Mills, Stuart J, Cowin, Allison J |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Angiogenesis
Inflammation wound healing Article Catalysis Mural cell pericytes Diabetes Complications Inorganic Chemistry lcsh:Chemistry Mice angiogenesis Downregulation and upregulation Diabetes Mellitus medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 Spectroscopy Cell Proliferation flightless I Gene knockdown biology diabetes Microfilament Proteins Organic Chemistry General Medicine Diabetic Foot Computer Science Applications Cell biology Cytoskeletal Proteins medicine.anatomical_structure lcsh:Biology (General) lcsh:QD1-999 inflammation Trans-Activators biology.protein Pericyte medicine.symptom Wound healing Platelet-derived growth factor receptor |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 5599, p 5599 (2020) International Journal of Molecular Sciences Volume 21 Issue 16 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Pericytes are peri-vascular mural cells which have an important role in the homeostatic regulation of inflammatory and angiogenic processes. Flightless I (Flii) is a cytoskeletal protein involved in regulating cellular functions, but its involvement in pericyte activities during wound healing is unknown. Exacerbated inflammation and reduced angiogenesis are hallmarks of impaired diabetic healing responses, and strategies aimed at regulating these processes are vital for improving healing outcomes. To determine the effect of altering Flii expression on pericyte function, in vitro and in vivo studies were performed to assess the effect on healing, inflammation and angiogenesis in diabetic wounds. Here, we demonstrated that human diabetic wounds display upregulated expression of the Flii protein in conjunction with a depletion in the number of platelet derived growth factor receptor &beta (PDGFR&beta ) +/ neural glial antigen 2 (NG2) + pericytes present in the dermis. Human pericytes were found to be positive for Flii and attenuating its expression in vitro through siRNA knockdown led to enhanced proliferation, migration and angiogenic functions. Genetic knockdown of Flii in a streptozotocin-induced murine model of diabetes led to increased numbers of pericytes within the wound. This was associated with dampened inflammation, an increased rate of angiogenic repair and improved wound healing. Our findings show that Flii expression directly impacts pericyte functions, including proliferation, motility and angiogenic responses. This suggests that Flii regulation of pericyte function may be in part responsible for the changes in pericyte-related processes observed in diabetic wounds. |
| Databáze: | OpenAIRE |
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