Gene expression profiling of Lucilia sericata larvae extraction/secretion-treated skin wounds
GENE
Authors: Polat, Erdal; Aksoz, Ilayda; Arkan, Hulya; Coskunpinar, Ender; Akbas, Fahri; Onaran, Ilhan
Abstract
The larvae of Lucilia sericata have been successfully used as medicinal maggots in the healing of wounds. The excretion/secretion (ES) products of the larvae have been shown to efficiently debride wounds and help the healing process. The mechanisms underlying ES-induced wound healing are not yet completely understood. One of the intriguing questions is the role of ESs in modulating gene expression at the transcriptional level in the skin wound environment during the healing process. To address this question, a study was conducted in which the ES-induced gene expression profile in wound biopsies and ES-treated wounds of rat skin in comparison with control group was analyzed at the molecular level by monitoring the expression of genes associated with wound healing. The expression levels of 82 genes at 4, 7, and 10 days after wounding were determined using a PCR array system following cDNA synthesis. A comparison from wounds revealed that 38 mRNAs (>= 5-fold expression) were differentially expressed in the ES-treated skin. For 27 genes, the multiple-test corrected p-value was statistically significant (p <= 0.00061). The expression pattern of these mRNAs was also altered during a period of 10 days. Many of the upregulated or downregulated mRNAs with therapy were extracellular matrix, cell adhesion-related proteins and growth factors. The genes that have the highest fold change (>1000-fold) were Col1a2, Col4a1, Ctsk, Ccl7, Angpt1, Cd40lg, Egf and Itgb5. Several of these gene products might play key roles in ES-induced wound healing. These findings may provide new insight for an understanding of the therapeutic potential of ESs for wound healing. (C) 2014 Elsevier B.V. All rights reserved.
Genome-Wide CpG Island Methylation Profiles of Cutaneous Skin with and without HPV Infection
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: AL-Eitan, Laith N.; Alghamdi, Mansour A.; Tarkhan, Amneh H.; Al-Qarqaz, Firas A.
Abstract
HPV infection is one of the most commonly transmitted diseases among the global population. While it can be asymptomatic, non-genital HPV infection often gives rise to cutaneous warts, which are benign growths arising from the epidermal layer of the skin. This study aimed to produce a global analysis of the ways in which cutaneous wart formation affected the CpG island methylome. The Infinium MethylationEPIC BeadChip microarray was utilized in order to quantitatively interrogate CpG island methylation in genomic DNA extracted from 24 paired wart and normal skin samples. Differential methylation analysis was carried out by means of assigning a combined rank score using RnBeads. The 1000 top-ranking CpG islands were then subject to Locus Overlap Analysis (LOLA) for enrichment of genomic ranges, while signaling pathway analysis was carried out on the top 100 differentially methylated CpG islands. Differential methylation analysis illustrated that the most differentially methylated CpG islands in warts lay within the ITGB5, DTNB, RBFOX3, SLC6A9, and C2orf27A genes. In addition, the most enriched genomic region sets in warts were Sheffield's tissue-clustered DNase hypersensitive sites, ENCODE's segmentation and transcription factor binding sites, codex sites, and the epigenome sites from cistrome. Lastly, signaling pathway analysis showed that the GRB2, GNB1, NTRK1, AXIN1, and SKI genes were the most common regulators of the genes associated with the top 100 most differentially methylated CpG islands in warts. Our study shows that HPV-induced cutaneous warts have a clear CpG island methylation profile that sets them apart from normal skin. Such a finding could account for the temporary nature of warts and the capacity for individuals to undergo clinical remission.