A microarray analysis of temporal gene expression profiles in thermally injured human skin

Abstract

Partial-thickness burn injuries incite a multitude of responses which eventually culminate in cutaneous wound repair. We hypothesized that these events would evoke extensive alterations in gene expression thereby orchestrating the complexity of spatial and temporal events that characterize “normal” human wound healing. In the present study, gene expressions from partial-thickness areas at defined temporal periods (1-3 days, 4-6 days, and 7-18 days) after injury were compared to normal non-wounded skin. Gene alterations proved extensive (2,286 genes). Statistically significant alterations were noted among increased and decreased genes expressed in the 3 different temporal groupings. Our foundational data (based on samples from 45 individuals) provide a comprehensive molecular gene expression portrait of the cutaneous reparative responses that are initiated during the first 17 days after injury. Our efforts also represent an initial endeavor to move beyond the historically defined “morphological phases” of wound repair toward reporting molecular clues that define the temporal sequence of healing in human subjects. Further analysis of genes that are either modulated or remain non-modulated following injury to normal skin is expected to identify potential targets for therapeutic augmentation or silencing.

Toll-Like Receptor Signaling in Burn Wound Healing and Scarring

“…27 In addition, S100A12 was highly expressed in hypertrophic scar, 28 which occurs commonly after deep partial-thickness burns. And, S100A12 expression was elevated from postburn day 0-17 in the margins of partialthickness burn wounds in a clinical study 29 ( Fig. 3).…”

Human Wound-Healing Research: Issues and Perspectives for Studies Using Wide-Scale Analytic Platforms

“…Their results demonstrated dramatically different reactions to injury between skin and mucosal wounds. 19 In a study by Greco et al, 20 the gene expression profiles of thermally injured human skin were observed with microarrays. For the analysis, skin samples were…”

“…Greco et al found that the expressions of several hundreds of genes were significantly altered between groups, including many calcium-binding proteins, cytokeratins, and chemokines. 20 In one study, Deonarine et al 21 investigated gene expression changes in skin wounds by collecting punch biopsies before and after wounding from basal cell carcinoma patients. They concluded that the initial response to a cutaneous wound induces transcriptional activation of proinflammatory stimuli which may alert the host defense.…”

645 Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis

“…8d). Among 179 genes elevated by IMQ in 129/SvJ females, for example, 82 were correspondingly increased in burn wound margins (0-3 days post-injury) [51], whereas fewer (53) were elevated in psoriasis lesions (Fig. 8e).…”

“…Additional datasets incorporated into analyses include those from prior microarray studies of IMQ dermatitis in mice (GSE27628, GSE47607, GSE60804, GSE63684, GSE78057) [2,[20][21][22], human KCs treated with poly(I:C) (GSE21260) [46], human KCs treated with IL-17A (GSE12109, GSE24767, GSE27533, GSE32620, GSE36287, GSE52361, GSE53751), the Immunological Genome Project (IGP; GSE15907) [47,48], macroscopically normal human skin from control subjects without skin disease (n = 90 subjects; GSE54456; Additional file 2), laser capture microdissected human suprabasal and basal epidermis (GSE42114) [49], regenerated human epidermis organotypic cultures (GSE52953) [50], Mediterranean spotted fever eschars (GSE32993), burn wound margins 0-3 days post-injury (GSE8056) [51], and Leishmania braziliensis-infected cutaneous lesions (GSE55664) [52]. Comparisons to 35 human skin diseases were made using a database of 124 expression signatures compiled and described in a previous publication [45].…”