Gene expression profiling of cutaneous wound healing
Open accessAbstract
Background: Although the sequence of events leading to wound repair has been described at the cellular and, to a limited extent, at the protein level this process has yet to be fully elucidated. Genome wide transcriptional analysis tools promise to further define the global picture of this complex progression of events. Study Design: This study was part of a placebo-controlled double-blind clinical trial in which basal cell carcinomas were treated topically with an immunomodifier – toll-like receptor 7 agonist: imiquimod. The fourteen patients with basal cell carcinoma in the placebo arm of the trial received placebo treatment consisting solely of vehicle cream. A skin punch biopsy was obtained immediately before treatment and at the end of the placebo treatment (after 2, 4 or 8 days). 17.5K cDNA microarrays were utilized to profile the biopsy material. Results: Four gene signatures whose expression changed relative to baseline (before wound induction by the pre-treatment biopsy) were identified. The largest group was comprised predominantly of inflammatory genes whose expression was increased throughout the study. Two additional signatures were observed which included preferentially pro-inflammatory genes in the early post-treatment biopsies (2 days after pre-treatment biopsies) and repair and angiogenesis genes in the later (4 to 8 days) biopsies. The fourth and smallest set of genes was down-regulated throughout the study. Early in wound healing the expression of markers of both M1 and M2 macrophages were increased, but later M2 markers predominated. Conclusion: The initial response to a cutaneous wound induces powerful transcriptional activation of pro-inflammatory stimuli which may alert the host defense. Subsequently and in the absence of infection, inflammation subsides and it is replaced by angiogenesis and remodeling. Understanding this transition which may be driven by a change from a mixed macrophage population to predominately M2 macrophages, may help the interpretation of the cellular and molecular events occurring in the microenvironment of serially biopsied tissues.
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Regenerative properties of microglia/macrophages following injury to muscle and skin are associated with alternative or deactivation to M2-polarized phenotypes (M2a and M2c, respectively).
“Regenerative properties of microglia/macrophages following injury to muscle6, 7 and skin8 are associated with alternative or deactivation to M2-polarized phenotypes (M2a and M2c, respectively), which secrete anti-inflammatory cytokines/growth factors9.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [8]
For the skin-injury portion cited to this paper, the Results (Comparison of markers of M1 and M2 macrophages; page not provided) report predominantly M2 markers later in cutaneous wound healing. The Discussion links M2 macrophages to tissue repair and angiogenesis, but does not identify the skin-associated phenotype as M2c or establish that a shift to M2 causes regeneration. The muscle-injury citations are separate from this source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA switch from M1- to M2-associated gene expression has been reported during cutaneous wound healing but has not been observed in studies of immune-mediated and toxin (cuprizone)-induced demyelination.
“A switch from M1- to M2-associated gene expression has been reported during cutaneous wound healing8 but has not been observed in studies of immune-mediated36 and toxin (cuprizone)-induced demyelination37.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [8]
In a study of human cutaneous wound healing, two gene clusters associated with M1/M2 polarization were transiently upregulated: an early cluster with mixed M1 and M2 genes (11 M1, 7 M2) and a later cluster predominantly M2 (1 M1, 9 M2).
“Of note, however, investigators identified two clusters of genes, associated with macrophage M1/ M2 polarization, which were upregulated transiently during the wound healing process.”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [105]
Treatment of rats, mice, and pigs with GHK effectively activates systemic healing throughout the animal.
“The treatment of rats, mice, and pigs with GHK was shown to effectively activate systemic healing throughout the animal.”
From GHK and DNA: Resetting the human genome to health (2014) · cites this paper as [40]
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- Authors
- Deonarine, K., Panelli, M. C., Stashower, M. E., Jin, P., Smith, K., Slade, H. B., Norwood, C., Wang, E., Marincola, F. M., & Stroncek, D. F.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Stroncek, David F
- Venue
- Journal of Translational Medicine
- Published
- 2007-02-21
- Volume
- 5
- Issue
- 1
- Pages
- 11-11
- ISSN
- 1479-5876 (ISSN-L)
- PMC
- PMC1804259
- OpenAlex
- W1594905954
- Cited by
- 229
- References
- 29
- Citations by year
- 2025: 6 · 2024: 6 · 2023: 9 · 2022: 30 · 2021: 7 · 2020: 9 · 2019: 7 · 2018: 10 · 2017: 10 · 2016: 16 · 2015: 17 · 2014: 19 · 2013: 23 · 2012: 18
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Translational Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
- Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
- Keywords
- skin wound healing, basal cell carcinoma, imiquimod, Toll-like receptor 7 agonist, gene expression profiling, inflammatory gene signature, M1/M2 macrophages, angiogenesis, tissue remodeling, skin biopsy, topical immunotherapy
- MeSH terms
- Imiquimod, Administration, Topical, Aminoquinolines, Biopsy, Humans, Macrophages, Placebos, Skin, Wound Healing, Biomarkers, Gene Expression Regulation, Neoplastic, Cluster Analysis, Gene Expression Profiling
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