Early Gene Expression in Wounded Human Keratinocytes Revealed by DNA Microarray Analysis (original) (raw)

Gene expression profiling of cutaneous wound healing

Journal of translational medicine, 2007

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. 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. Four gene signatures whose expression changed relative to baseline (before wound induction by the pre-treatment biopsy) were identified. The largest group was...

Cellular and Molecular Processes in Wound Healing

Biomedicines, 2023

This review summarizes the recent knowledge of the cellular and molecular processes that occur during wound healing. However, these biological mechanisms have yet to be defined in detail; this is demonstrated by the fact that alterations of events to pathological states, such as keloids, consisting of the excessive formation of scars, have consequences yet to be defined in detail. Attention is also dedicated to new therapies proposed for these kinds of pathologies. Awareness of these scientific problems is important for experts of various disciplines who are confronted with these kinds of presentations daily.

Cellular Mechanisms and Therapies in Wound Healing: Looking toward the Future

Biomedicines

The high professionalism of these publications consists, on the one hand, of revealing some of the mechanisms underlying wound healing and, on the other hand, of proposing alternative therapies for the fine control of inflammation following injury to avoid fibrotic scars or impaired wounds [...]

Application of mitogen-activated protein kinase inhibitor SP 600125 for wound healing control

Abstract Background: The problem of wound healing remains critical due to lack of methods for direct control of regeneration processes. Main purpose of the study: To investigate the ability to control wound healing process by inhibiting JNK mitogenactivated protein kinase. Methods: Skin-muscle wounds were made to Wistar rats 9 months old, 220-250 g weight. Two groups were examined, each one consisted of 30 animals: control group (inoculation of placebo plate); JNK group (inoculation of the inhibitor of JNK MAPK cascade SP 600125, the dosage per one animal was 2,6 μg/kg delivered in the form of original medicated film). The animals were taken out of the experiment in the periods from 2 hours up to 30 days. The segments of the skin-muscle wound were subjected to histological, immunohistochemical (staining for Col1A1, actin, CD34) and immunofluorescent (staining for CD34, CD45, ММР9) investigations. We measured the ratio of section area occupied by collagen fibers to the total area of tissue in micrographs our proposed method. The analysis of the contingence tables and Mann–Whitney U test were used during the investigation. Results: The study revealed that application of JNK MAPK inhibitor alters the wound healing process considerably, stimulates early generation of connective tissue, increases its production rate and accelerates maturation of connective tissue in the wound area. Application of JNK MAPK inhibitor impacts considerably marker expression of various fibroblasts, causing higher expression of their marrow precursors in the focus, which is indicative of more active attraction of progenitor cells into the connective tissue generation zone. Early application of JNK MAPK inhibitor increases quantity of myofibroblasts in the wound and increases expression of procollagen in fibroblasts located in the zone of connective tissue formation. The risk of keloid scarring remains small because there is an early completion of the scar formation and in this area there no cells that are capable for prolonged intensive collagen synthesis. The results enable to consider local inhibition of JNK MAPK cascade associated with a wound process to be a prospective approach to acceleration of surgical wound healing. Conclusions: It has thus been established that the application of MAPK inhibitor considerably affects marker expression of various fibroblasts, which increases the expression of marrow precursors in the focus, being indicative of a more active attraction of progenitor cells into connective tissue formation zone. The developed original method of local application of JNK MAPK inhibitor SP 600125 to surgical wound, which enables to modify the surgical wound healing process with a single application, is recommended for pre-clinical and clinical trials for further wide clinical application. Keywords: Connective tissue, JNK mitogen-activated protein kinases, wounds and injuries

p38 MAPK inhibition reduces diabetes-induced impairment of wound healing

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2009

In healthy tissue, a wound initiates an inflammatory response characterized by the presence of a hematoma, infiltration of inflammatory cells into the wound and, eventually, wound healing. In pathological conditions like diabetes mellitus, wound healing is impaired by the presence of chronic nonresolving inflammation. p38 mitogen-activated protein kinase (MAPK) inhibitors have demonstrated anti-inflammatory effects, primarily by inhibiting the expression of inflammatory cytokines and regulating cellular traffic into wounds. The db/db mouse model of type 2 diabetes was used to characterize the time course of expression of activated p38 during impaired wound healing. The p38α-selective inhibitor, SCIO-469, was applied topically and effects on p38 activation and on wound healing were evaluated. A topical dressing used clinically, Promogran TM , was used as a comparator. In this study, we established that p38 is phosphorylated on Days 1 to 7 post-wounding in db/db mice. Further, we demonstrated that SCIO-469, at a dose of 10 µg/wound, had a positive effect on wound contraction, granulation tissue formation, and re-epithelialization, and also increased wound maturity during healing. These effects were similar to or greater than those observed with Promogran TM. These results suggest a novel approach to prophylactic and therapeutic management of chronic wounds associated with diabetes or other conditions in which healing is impaired.

Gene Expression Linked to Reepithelialization of Human Skin Wounds

International Journal of Molecular Sciences

Our understanding of the regulatory processes of reepithelialization during wound healing is incomplete. In an attempt to map the genes involved in epidermal regeneration and differentiation, we measured gene expression in formalin-fixed, paraffin-embedded standardized epidermal wounds induced by the suction-blister technique with associated nonwounded skin using NanoString technology. The transcripts of 139 selected genes involved in clotting, immune response to tissue injury, signaling pathways, cell adhesion and proliferation, extracellular matrix remodeling, zinc transport and keratinocyte differentiation were evaluated. We identified 22 upregulated differentially expressed genes (DEGs) in descending order of fold change (MMP1, MMP3, IL6, CXCL8, SERPINE1, IL1B, PTGS2, HBEGF, CXCL5, CXCL2, TIMP1, CYR61, CXCL1, MMP12, MMP9, HGF, CTGF, ITGB3, MT2A, FGF7, COL4A1 and PLAUR). The expression of the most upregulated gene, MMP1, correlated strongly with MMP3 followed by IL6 and IL1B. rhI...

Early gene expression profile of human skin to injury using high-density cDNA microarrays

Wound Repair and Regeneration, 2001

Disturbances in normal wound healing may be traced to perturbations in gene expression following injury. To decipher normal and abnormal genetic responses to cutaneous injury, baseline gene expression of uninjured skin and injured skin must be better defined. Our aim for this study was to determine the gene expression profile of human skin immediately following injury using cDNA microarrays. Samples of normal and injured skin were obtained from 5 healthy females undergoing breast reduction surgery. Specimens of the epidermis and dermis were obtained at 30 minutes and 1 hour after the initial injury. RNA was extracted, reverse transcribed into cDNA and hybridized onto high-density cDNA microarray membranes of 4,000 genes. At 30 minutes, injury resulted in a consistent increase (> ‫)ן2‬ in gene expression of 124 out of 4,000 genes (3%). These genes were primarily involved in transcription and signaling. None of the 4,000 genes were decreased (< ‫)ן2‬ at 30 minutes. At 1 hour only 46 out of the 4,000 genes were increased in expression (1.15%) but 264 out of 4,000 (6.6%) genes were decreased greater than 2 fold, indicating a silencing of many structural genes. We have identified several genes, namely, suppressor of cytokine signaling-1, rho HP1, and BB1, that are highly expressed after injury and may have an unappreciated role in regulating the initial inflammatory response. These data provide an initial high-throughput analysis of gene expression immediately following human skin injury and show the utility and future importance of high-throughput analysis in skin biology and wound repair. (WOUND REP REG 2001;9:360-370) Response to dermal injury comprises multiple cellular cDNA Complementary DNA and extracellular events. These events include coagula-From the Department of Surgery, VA Puget Sound Health tients who heal normally versus those who develop hy-Care System, Harborview Medical Center & Unipertrophic scars or keloids. 2,3 To elucidate the different volved in cell-cell signaling including growth factors. 4,5 WA 98195. Fax: (206) 543-8136; Email: