Elevated Thrombospondin 2 Contributes to Delayed Wound Healing in Diabetes

Diabetes
Britta KunkemoellerT R Kyriakides

Abstract

Impaired wound healing is a major complication of diabetes, and despite the associated risks, treatment strategies for diabetic wounds remain limited. This is due, in part, to an incomplete understanding of the underlying pathological mechanisms, including the effects of hyperglycemia on components of the extracellular matrix (ECM). In the current study, we explored whether the expression of thrombospondin 2 (TSP2), a matricellular protein with a demonstrated role in response to injury, was associated with delayed healing in diabetes. First, we found that TSP2 expression was elevated in diabetic mice and skin from patients with diabetes. Then, to determine the contribution of TSP2 to impaired healing in diabetes, we developed a novel diabetic TSP2-deficient model. Though the TSP2-deficient mice developed obesity and hyperglycemia comparable with diabetic control mice, they exhibited significantly improved healing, characterized by accelerated reepithelialization and increased granulation tissue formation, fibroblast migration, and blood vessel maturation. We further found that hyperglycemia increased TSP2 expression in fibroblasts, the major cellular source of TSP2 in wounds. Mechanistically, high glucose increased activation o...Continue Reading

References

Nov 26, 1999·The Journal of Investigative Dermatology·T R KyriakidesP Bornstein
May 6, 2003·Circulation Research·Vesna StepanovicGina C Schatteman
Nov 18, 2005·Lancet·Andrew J M BoultonJan Apelqvist
Nov 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Won Ho YangJin Won Cho
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Susan MacLauchlanThemis R Kyriakides
Feb 23, 2012·British Journal of Pharmacology·Aileen J F King
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·David F AllisonMarty W Mayo
Feb 8, 2013·Acta Ophthalmologica·Ahmed M Abu El-AsrarKarel Geboes
Jun 1, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Ok-Nam BaeAlex F Chen
Jan 21, 2014·Biochimica Et Biophysica Acta·Nicole E CalabroThemis R Kyriakides
Apr 29, 2014·BioMed Research International·Pawel OlczykKatarzyna Komosinska-Vassev
Nov 26, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ming GaoMayland Chang
Mar 19, 2016·Advances in Wound Care·Lauren E TracyE J Caterson
Apr 2, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mayland Chang
Nov 15, 2018·ACS Applied Materials & Interfaces·Aaron H MorrisThemis R Kyriakides

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Citations

Sep 20, 2020·The Journal of Pharmacology and Experimental Therapeutics·A GiulianiL Calzà
Feb 26, 2021·Oxidative Medicine and Cellular Longevity·Liling DengWuquan Deng
Feb 6, 2021·Matrix Biology Plus·Yaqing Huang, Themis R Kyriakides

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