Characterization of the acute temporal changes in excisional murine cutaneous wound inflammation by screening of the wound-edge transcriptome

Abstract

This work represents a maiden effort to systematically screen the transcriptome of the healing wound-edge tissue temporally using high-density GeneChips. Changes during the acute inflammatory phase of murine excisional wounds were characterized histologically. Sets of genes that significantly changed in expression during healing could be segregated into the following five sets: up-early (6-24 h; cytokine-cytokine receptor interaction pathway), up-intermediary (12-96 h; leukocyte-endothelial interaction pathway), up-late (48-96 h; cell-cycle pathway), down-early (6-12 h; purine metabolism) and down-intermediary (12-96 h; oxidative phosphorylation pathway). Results from microarray and real-time PCR analyses were consistent. Results listing all genes that were significantly changed at any specific time point were further mined for cell-type (neutrophils, macrophages, endothelial, fibroblasts, and pluripotent stem cells) specificity. Candidate genes were also clustered on the basis of their functional annotation, linking them to inflammation, angiogenesis, reactive oxygen species (ROS), or extracellular matrix (ECM) categories. Rapid induction of genes encoding NADPH oxidase subunits and downregulation of catalase in response to wounding is consistent with the fact that low levels of endogenous H2O2 is required for wound healing. Angiogenic genes, previously not connected to cutaneous wound healing, that were induced in the healing wound-edge included adiponectin, epiregulin, angiomotin, Nogo, and VEGF-B. This study provides a digested database that may serve as a valuable reference tool to develop novel hypotheses aiming to elucidate the biology of cutaneous wound healing comprehensively.

Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds

“…1 C and D). Infiltration of macrophages into the wound site represents a key component of the acute inflammatory phase of wound healing (13). With the goal to study the inflammatory response to wounding, macrophages in the tissue sections were detected on day-3 wound sections using the panmacrophage marker F4/80.…”

“…Consistently, the ischemic wounds were hypoxic. Adult cutaneous tissue repair is accompanied by a robust recruitment of inflammatory cells to the wound site (13).…”

“…All studies were performed in compliance with the Institutional Animal Care and Use Committee of Ohio State University. Mice were housed individually after wounding with a 12-h light/ dark cycle and temperature in the institutional animal facilities, and allowed access to food and water ad libitum, as described previously (13).…”

The effect of exercise and oxidant–antioxidant intervention on the levels of neurotrophins and free radicals in spinal cord of rats

“…It is known that ROS, but especially H 2 O 2 , have a concentration-dependent diverse effect on the spinal cord and at high concentrations they can induce apoptosis and serious cell damage, 5 although recent findings suggest that low levels of endogenous H 2 O 2 is required for wound healing in different tissues. 6 In addition, oxidative challenge, such as ischemic preconditioning, has been shown to attenuate oxidative stress in the spinal cord. 7 Preconditioning involves the induction of GDNF, which appears to promote axonal growth of injury-primed sensory neurons in a concentration-dependent manner.…”

miRNA Control of Tissue Repair and Regeneration

“…Injury-responsive coding genes are recognized as a main driver of wound healing and tissue regeneration. 1 After injury, tissue healing is initiated either by regeneration or repair or by a combination of both. Although robust tissue regeneration is observed in certain lower vertebrates, including urodele amphibians and teleost fish, mammalian tissue regeneration is limited, particularly in adults.…”