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dc.contributor.authorAl-Rikabi, Aaiad H.A.
dc.contributor.authorTobin, Desmond J.
dc.contributor.authorRiches-Suman, Kirsten
dc.contributor.authorThornton, M. Julie
dc.date.accessioned2021-03-31T16:32:20Z
dc.date.accessioned2021-04-16T11:08:19Z
dc.date.available2021-03-31T16:32:20Z
dc.date.available2021-04-16T11:08:19Z
dc.date.issued2021-01
dc.identifier.citationAl-Rikabi AHA, Tobin DJ, Riches-Suman K et al (2021) Dermal fibroblasts cultured from donors with type 2 diabetes mellitus retain an epigenetic memory associated with poor wound healing responses. Scientific Reports. 11: 1474.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18438
dc.descriptionYesen_US
dc.description.abstractThe prevalence of Type 2 diabetes mellitus (T2DM) is escalating globally. Patients suffer from multiple complications including the development of chronic wounds that can lead to amputation. These wounds are characterised by an inflammatory environment including elevated tumour necrosis factor alpha (TNF-α). Dermal fibroblasts (DF) are critical for effective wound healing, so we sought to establish whether there were any differences in DF cultured from T2DM donors or those without diabetes (ND-DF). ND- and T2DM-DF when cultured similarly in vitro secreted comparable concentrations of TNF-α. Functionally, pre-treatment with TNF-α reduced the proliferation of ND-DF and transiently altered ND-DF morphology; however, T2DM-DF were resistant to these TNF-α induced changes. In contrast, TNF-α inhibited ND- and T2DM-DF migration and matrix metalloprotease expression to the same degree, although T2DM-DF expressed significantly higher levels of tissue inhibitor of metalloproteases (TIMP)-2. Finally, TNF-α significantly increased the secretion of pro-inflammatory cytokines (including CCL2, CXCL1 and SERPINE1) in ND-DF, whilst this effect in T2DM-DF was blunted, presumably due to the tendency to higher baseline pro-inflammatory cytokine expression observed in this cell type. Collectively, these data demonstrate that T2DM-DF exhibit a selective loss of responsiveness to TNF-α, particularly regarding proliferative and secretory functions. This highlights important phenotypic changes in T2DM-DF that may explain the susceptibility to chronic wounds in these patients.en_US
dc.description.sponsorshipThis study was funded by an Iraqi government studentship to AHAA-R.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1038/s41598-020-80072-zen_US
dc.rights© The Author(s) 2021. Open Access Tis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.en_US
dc.subjectBiomarkersen_US
dc.subjectCell biologyen_US
dc.subjectType 2 diabetes mellitus (T2DM)en_US
dc.subjectDermal fibroblastsen_US
dc.subjectWound healingen_US
dc.subjectChronic woundsen_US
dc.titleDermal fibroblasts cultured from donors with type 2 diabetes mellitus retain an epigenetic memory associated with poor wound healing responsesen_US
dc.status.refereedYesen_US
dc.date.Accepted2020-12-02
dc.date.application2021-01-14
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.date.updated2021-03-31T15:32:22Z
refterms.dateFOA2021-04-16T11:08:46Z
dc.openaccess.statusGolden_US


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