Diabetic wound healing: The impact of diabetes on myofibroblast activity and its potential therapeutic treatments
- PMID: 34157786
- DOI: 10.1111/wrr.12954
Diabetic wound healing: The impact of diabetes on myofibroblast activity and its potential therapeutic treatments
Abstract
Diabetes is a systemic disease in which the body cannot regulate the amount of sugar, namely glucose, in the blood. High glucose toxicity has been implicated in the dysfunction of diabetic wound healing, following insufficient production (Type 1) or inadequate usage (Type 2) of insulin. Chronic non-healing diabetic wounds are one of the major complications of both types of diabetes, which are serious concerns for public health and can impact the life quality of patients significantly. In general, diabetic wounds are characterized by deficient chemokine production, an unusual inflammatory response, lack of angiogenesis and epithelialization, and dysfunction of fibroblasts. Increasing scientific evidence from available experimental studies on animal and cell models strongly associates impaired wound healing in diabetes with dysregulated fibroblast differentiation to myofibroblasts, interrupted myofibroblast activity, and inadequate extracellular matrix production. Myofibroblasts play an important role in tissue repair by producing and organizing extracellular matrix and subsequently promoting wound contraction. Based on these studies, hyperglycaemic conditions can interfere with cytokine signalling pathways (such as growth factor-β pathway) affecting fibroblast differentiation, alter fibroblast apoptosis, dysregulate dermal lipolysis, and enhance hypoxia damage, thus leading to damaged microenvironment for myofibroblast formation, inappropriate extracellular matrix modulation, and weakened wound contraction. In this review, we will focus on the current available studies on the impact of diabetes on fibroblast differentiation and myofibroblast function, as well as potential treatments related to the affected pathways.
Keywords: M2 phenotype macrophage; chronic wounds; extracellular matrix; fibroblast-to-myofibroblast differentiation; myofibroblast.
© 2021 The Wound Healing Society.
Similar articles
-
Dynamic Histological Events and Molecular Changes in Excisional Wound Healing of Diabetic DB/DB Mice.J Surg Res. 2019 Jun;238:186-197. doi: 10.1016/j.jss.2019.01.048. Epub 2019 Feb 13. J Surg Res. 2019. PMID: 30771688
-
Macrophage Phenotypes Regulate Scar Formation and Chronic Wound Healing.Int J Mol Sci. 2017 Jul 17;18(7):1545. doi: 10.3390/ijms18071545. Int J Mol Sci. 2017. PMID: 28714933 Free PMC article. Review.
-
Myofibroblast progeny in wound biology and wound healing studies.Wound Repair Regen. 2021 Jul;29(4):531-547. doi: 10.1111/wrr.12937. Epub 2021 May 31. Wound Repair Regen. 2021. PMID: 34009713 Review.
-
Featured Article: TGF-β1 dominates extracellular matrix rigidity for inducing differentiation of human cardiac fibroblasts to myofibroblasts.Exp Biol Med (Maywood). 2018 Apr;243(7):601-612. doi: 10.1177/1535370218761628. Epub 2018 Mar 4. Exp Biol Med (Maywood). 2018. PMID: 29504479 Free PMC article.
-
Proapoptotic effect of control-released basic fibroblast growth factor on skin wound healing in a diabetic mouse model.Wound Repair Regen. 2016 Jan-Feb;24(1):65-74. doi: 10.1111/wrr.12375. Epub 2015 Nov 4. Wound Repair Regen. 2016. PMID: 26488443
Cited by
-
Mesenchymal stem cells-based drug delivery systems for diabetic foot ulcer: A review.World J Diabetes. 2023 Nov 15;14(11):1585-1602. doi: 10.4239/wjd.v14.i11.1585. World J Diabetes. 2023. PMID: 38077806 Free PMC article. Review.
-
Targeting DNA methylation and demethylation in diabetic foot ulcers.J Adv Res. 2023 Dec;54:119-131. doi: 10.1016/j.jare.2023.01.009. Epub 2023 Jan 25. J Adv Res. 2023. PMID: 36706989 Free PMC article. Review.
-
Targeting Wnt/β-catenin signaling and its interplay with TGF-β and Notch signaling pathways for the treatment of chronic wounds.Cell Commun Signal. 2024 Apr 26;22(1):244. doi: 10.1186/s12964-024-01623-9. Cell Commun Signal. 2024. PMID: 38671406 Free PMC article. Review.
-
Analysis of risk factors affecting the postoperative drainage after a laparoscopic partial nephrectomy: a retrospective study.Front Med (Lausanne). 2024 Jan 24;11:1327882. doi: 10.3389/fmed.2024.1327882. eCollection 2024. Front Med (Lausanne). 2024. PMID: 38327705 Free PMC article.
-
PDK4 rescues high-glucose-induced senescent fibroblasts and promotes diabetic wound healing through enhancing glycolysis and regulating YAP and JNK pathway.Cell Death Discov. 2023 Nov 25;9(1):424. doi: 10.1038/s41420-023-01725-2. Cell Death Discov. 2023. PMID: 38001078 Free PMC article.
References
REFERENCES
-
- Chapple IL, Genco R. Working group 2 of joint EFP/AAP workshop. Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol. 2013;40(14):S106-S112.
-
- International Diabetes Federation. IDF Diabetes Atlas. 9th ed. Brussels, Belgium: International Diabetes Federation; 2019.
-
- Falanga V. Wound healing and its impairment in the diabetic foot. Lancet. 2005;366(9498):1736-1743.
-
- Hinz B. The role of myofibroblasts in wound healing. Curr Res Transl Med. 2016;64(4):171-177.
-
- Hinz B, Lagares D. Evasion of apoptosis by myofibroblasts: a hallmark of fibrotic diseases. Nat Rev Rheumatol. 2020;16(1):11-31.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Medical