Dysregulated healing responses in diabetic wounds occur in the early stages postinjury

in Journal of Molecular Endocrinology
Authors:
Kiara Boodhoo Department of Medicine, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa

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Mare Vlok Central Analytical Facility, Proteomics Unit, Stellenbosch University, Cape Town, South Africa

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David L Tabb Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa
Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa
Bioinformatics Unit, South African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa

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Kathryn H Myburgh Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa

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Mari van de Vyver Department of Medicine, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa

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https://orcid.org/0000-0002-0861-2939

Correspondence should be addressed to M van de Vyver: vandevyverm@sun.ac.za
DOI:
https://doi.org/10.1530/JME-20-0256
Volume/Issue:
Volume 66: Issue 2
Article Type:
Research Article
Page Range:
141–155
Online Publication Date:
Feb 2021
Copyright:
© 2021 Society for Endocrinology 2021
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Chronic wounds are a serious and debilitating complication of diabetes. A better understanding of the dysregulated healing responses following injury will provide insight into the optimal time frame for therapeutic intervention. In this study, a direct comparison was done between the healing dynamics and the proteome of acute and obese diabetic wounds on days 2 and 7 following injury. Full thickness excisional wounds were induced on obese diabetic (B6.Cg-lepob/J, ob/ob, n = 14) (blood glucose 423.25 ± 127.92 mg/dL) and WT control (C57BL/6J, n = 14) (blood glucose 186.67 ± 24.5 mg/dL) mice. Histological analysis showed no signs of healing in obese DM wounds whereas complete wound closure/re-epithelisation, the formation of granulation tissue and signs of re-vascularisation, was evident in acute wounds on day 7. In obese DM wounds, substance P deficiency and increased MMP-9 activity on day 2 coincided with increased cytokine/chemokine levels within wound fluid. LC-MS/MS identified 906 proteins, of which 23 (Actn3, Itga6, Epb41, Sncg, Nefm, Rsp18, Rsp19, Rpl22, Macroh2a1, Rpn1, Ppib, Snrnp70, Ddx5, Eif3g, Tpt1, FABP5, Cavin1, Stfa1, Stfa3, Cycs, Tkt, Mb, Chmp2a) were differentially expressed in wounded tissue on day 2 (P < 0.05; more than two-fold) and 6 (Cfd, Ptms, Hp, Hmga1, Cbx3, Syap1) (P < 0.05; more than two-fold) on day 7. A large number of dysregulated proteins on day 2 was associated with an inability to progress into the proliferative stage of healing and suggest that early intervention might be pivotal for effective healing outcomes. The proteomic approach highlighted the complexity of obese DM wounds in which the dysregulation involves multiple regulatory pathways and biological processes.

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Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© 2021 Society for Endocrinology 2021
Page(s):
15
Article Type:
Research Article
Received Date:
03 Nov 2020
Accepted Date:
16 Dec 2020
Print Publication Date:
01 Feb 2021
Online Publication Date:
Feb 2021
Keywords:
wound healing; diabetes; inflammation; substance P

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