Diabetes-impaired wound healing and altered macrophage activation: a possible pathophysiologic correlation
Abstract
Macrophages play a critical role in wound healing and can be activated to two distinctive phenotypes in vitro: classical macrophage activation (caM) and alternative macrophage activation (aaM). This study investigated whether the impaired cutaneous repair observed in streptozotocin-induced diabetic rats was associated with altered macrophage activation. Our results show that macrophage activation phenotypes could be observed in wound healing through double immunostaining. The caM macrophages appeared in the initial stage of wound healing, followed by aaM macrophages, which predominated in normal wounds. However, through examining markers associated with activation by immunoblotting and real-time polymerase chain reaction (PCR), diabetic wounds demonstrated insufficient caM in the early stage but excessive aaM in the later proliferative phase. Moreover, the macrophage activation markers were correlated with the instructive T helper cell type 1 (Th1)/Th2 cytokines in both groups. It was indicated that changed macrophage activation might contribute to impaired healing in diabetes wounds, and that strategies for reverting this abnormal activation could be useful for enhancing the wound healing process.
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IL-4 gene expression is elevated from 1 to 7 days in rat skin wounds, and protein expression is elevated between 12 h and 10 days in human skin wounds.
“However, IL-4 gene expression is elevated from 1 to 7 days in rat skin wounds [56], and protein expression is elevated between 12 h and 10 days in human skin wounds (peak ϳ12 pg/mg protein in injured skin vs. nearly undetectable in uninjured) [58]; IL-4 protein is present at similar levels in infarcted rat myocardium [72].”
From Macrophage phenotypes during tissue repair (2013) · cites this paper as [56]
After excisional skin wounding in rats or photochemical liver injury in mice, only a fraction of the wound Mp expresses iNOS (10-15% positive at peak in skin).
“After excisional skin wounding in rats [56] or photochemical liver injury in mice [68], only a fraction of the wound Mp expresses iNOS (10 -15% positive at peak in skin), and the heterogeneity of the Mp population may be dependent on proximity to the injured site [68].”
From Macrophage phenotypes during tissue repair (2013) · cites this paper as [56]
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- Authors
- Miao, M., Niu, Y., Xie, T., Yuan, B., Qing, C., & Lu, S.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Lu, Shuliang
- Venue
- Wound Repair and Regeneration
- Publisher
- Wiley
- Published
- 2012-03
- Volume
- 20
- Issue
- 2
- Pages
- 203-213
- ISSN
- 1067-1927 (ISSN-L)
- 1524-475X
- OpenAlex
- W1878538572
- Cited by
- 125
- References
- 33
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 11 · 2023: 9 · 2022: 11 · 2021: 20 · 2020: 6 · 2019: 11 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 4 · 2014: 7 · 2013: 7 · 2012: 3
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Wound Repair and Regeneration (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- School of Medicine, Shanghai Jiao Tong University
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- diabetes mellitus, delayed wound healing, macrophage activation, M1 macrophage polarization, alternative macrophage activation, skin wound healing, streptozotocin-induced diabetes, Th1/Th2 cytokines
- MeSH terms
- Animals, Diabetes Mellitus, Experimental, Immunohistochemistry, Macrophage Activation, Male, Phenotype, Skin, Wound Healing, Blotting, Western, Interleukin-10, Rats, Sprague-Dawley, Interleukin-12, Rats, Real-Time Polymerase Chain Reaction
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