Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds
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 unk...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/16/5599 |
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| author | Hannah M Thomas Parinaz Ahangar Benjamin R Hofma Xanthe L Strudwick Robert Fitridge Stuart J Mills Allison J Cowin |
| author_facet | Hannah M Thomas Parinaz Ahangar Benjamin R Hofma Xanthe L Strudwick Robert Fitridge Stuart J Mills Allison J Cowin |
| author_sort | Hannah M Thomas |
| collection | DOAJ |
| description | 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 β (PDGFRβ) +/ 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 <i>Flii</i> 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. |
| first_indexed | 2024-03-10T17:57:40Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T17:57:40Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-24be14aa8cb64d4882eb4f52b2589f512023-11-20T09:07:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116559910.3390/ijms21165599Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic WoundsHannah M Thomas0Parinaz Ahangar1Benjamin R Hofma2Xanthe L Strudwick3Robert Fitridge4Stuart J Mills5Allison J Cowin6Future Industries Institute, University of South Australia, Adelaide 5000, AustraliaFuture Industries Institute, University of South Australia, Adelaide 5000, AustraliaFuture Industries Institute, University of South Australia, Adelaide 5000, AustraliaFuture Industries Institute, University of South Australia, Adelaide 5000, AustraliaFaculty of Health and Medical Sciences, University of Adelaide, Adelaide 5000, AustraliaFuture Industries Institute, University of South Australia, Adelaide 5000, AustraliaFuture Industries Institute, University of South Australia, Adelaide 5000, AustraliaPericytes 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 β (PDGFRβ) +/ 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 <i>Flii</i> 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.https://www.mdpi.com/1422-0067/21/16/5599pericytesdiabetesflightless Iangiogenesisinflammationwound healing |
| spellingShingle | Hannah M Thomas Parinaz Ahangar Benjamin R Hofma Xanthe L Strudwick Robert Fitridge Stuart J Mills Allison J Cowin Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds International Journal of Molecular Sciences pericytes diabetes flightless I angiogenesis inflammation wound healing |
| title | Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds |
| title_full | Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds |
| title_fullStr | Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds |
| title_full_unstemmed | Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds |
| title_short | Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds |
| title_sort | attenuation of flightless i increases human pericyte proliferation migration and angiogenic functions and improves healing in murine diabetic wounds |
| topic | pericytes diabetes flightless I angiogenesis inflammation wound healing |
| url | https://www.mdpi.com/1422-0067/21/16/5599 |
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