{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:02:24Z","timestamp":1779930144286,"version":"3.53.1"},"reference-count":29,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T00:00:00Z","timestamp":1596585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT#1002009"],"award-info":[{"award-number":["GNT#1002009"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Commonwealth Government","award":["Scholarship"],"award-info":[{"award-number":["Scholarship"]}]},{"DOI":"10.13039\/100008943","name":"Playford Trust","doi-asserted-by":"publisher","award":["Scholarship"],"award-info":[{"award-number":["Scholarship"]}],"id":[{"id":"10.13039\/100008943","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cell Therapy Manufacturing Cooperative Research Centre","award":["2-11"],"award-info":[{"award-number":["2-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03b2 (PDGFR\u03b2) +\/ 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.<\/jats:p>","DOI":"10.3390\/ijms21165599","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T06:02:21Z","timestamp":1596607341000},"page":"5599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds"],"prefix":"10.3390","volume":"21","author":[{"given":"Hannah M","family":"Thomas","sequence":"first","affiliation":[{"name":"Future Industries Institute, University of South Australia, Adelaide 5000, Australia"},{"name":"Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia"},{"name":"Cell Therapy Manufacturing Cooperative Research Centre, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-3501","authenticated-orcid":false,"given":"Parinaz","family":"Ahangar","sequence":"additional","affiliation":[{"name":"Future Industries Institute, University of South Australia, Adelaide 5000, Australia"},{"name":"Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia"},{"name":"Cell Therapy Manufacturing Cooperative Research Centre, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R","family":"Hofma","sequence":"additional","affiliation":[{"name":"Future Industries Institute, University of South Australia, Adelaide 5000, Australia"},{"name":"Cell Therapy Manufacturing Cooperative Research Centre, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8557-3857","authenticated-orcid":false,"given":"Xanthe L","family":"Strudwick","sequence":"additional","affiliation":[{"name":"Future Industries Institute, University of South Australia, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Fitridge","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2462-7081","authenticated-orcid":false,"given":"Stuart J","family":"Mills","sequence":"additional","affiliation":[{"name":"Future Industries Institute, University of South Australia, Adelaide 5000, Australia"},{"name":"Cell Therapy Manufacturing Cooperative Research Centre, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2885-2080","authenticated-orcid":false,"given":"Allison J","family":"Cowin","sequence":"additional","affiliation":[{"name":"Future Industries Institute, University of South Australia, Adelaide 5000, Australia"},{"name":"Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cmet.2012.11.012","article-title":"Vascular complications of diabetes: Mechanisms of injury and protective factors","volume":"17","author":"King","year":"2013","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1016\/S0140-6736(05)67698-2","article-title":"The global burden of diabetic foot disease","volume":"366","author":"Boulton","year":"2005","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.2337\/db12-0227","article-title":"Mechanisms involved in the development and healing of diabetic foot ulceration","volume":"61","author":"Dinh","year":"2012","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Thomas, H., Cowin, A., and Mills, S. 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