RNA-seq unravels distinct expression profiles of keloids and Dupuytren's disease.

Keloid scars and Dupuytren's disease are two common, chronic, and incurable fibroproliferative disorders that, among other shared clinical features, may induce joint contractures. We employed bulk RNA sequencing to discern potential shared gene expression patterns and underlying pathological pathways between these two conditions. Our aim was to uncover potential molecular targets that could pave the way for novel therapeutic strategies. Differentially expressed genes (DEGs) were functionally annotated using Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein-interaction (PPI) networks were constructed by using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. The Molecular Complex Detection (MCODE) plugin was used for downstream analysis of the PPI networks. A total of 1922 DEGs were identified within Dupuytren's and keloid samples, yet no overlapping gene expression profiles were detected. Significantly enriched GO terms were related to skin development and tendon formation in keloid scars and Dupuytren's disease, respectively. The PPI network analysis revealed 10 genes and the module analysis provided six protein networks, which might play an integral part in disease development. These genes, including CDH1, ERBB2, CASP3 and RPS27A, may serve as new targets for future research to develop biomarkers and/or therapeutic agents.

Systematic review of molecular pathways in burn wound healing.

Depending on extent and depth, burn injuries and resulting scars may be challenging and expensive to treat and above all heavily impact the patients' lives. This systematic review represents the current state of knowledge on molecular pathways activated during burn wound healing. All currently known molecular information about gene expression and molecular interactions in mammals has been summarized. An ample interaction of regenerative cytokines, growth factors, ECM-regenerative molecules and proinflammatory immune response became apparent. We identified three molecules to be most often involved in the pathways: TGFB1, ACTA1 and COL1A1. Yet, other factors including FLII, AKT1 and miR-145 were shown to play pivotal roles in burn wound healing as well. This systematic review helps to explain the fundamental molecular proceedings participating in burn wound healing. A number of new molecular interactions and functional connections were identified yielding intriguing new research targets. An interactive version of the first network about molecular pathways and interactions during burn wound healing is provided in the online edition and on WikiPathways.

Keloids are transcriptionally distinct from normal and hypertrophic scars.

Wound healing and skin regeneration after injury are complex biological processes, and deep injuries with a high degree of tissue destruction may result in severe scar formation. Clinically, scars can be classified into normal, hypertrophic and keloid scars. However, the molecular signature of each scar type is currently not known. The aim of this study was to reveal the transcriptional landscape of normal, hypertrophic and keloid skin scars following hand and plastic surgery based on total RNA sequencing. Eighteen skin scar samples from hand and plastic surgeries of human donors were minced directly after removal and stored in TRIzol (Thermo Fisher, USA). Samples were then subjected to RNA isolation, cDNA library preparation, bulk RNA sequencing and bioinformatics analysis. We show that keloid scars transcriptionally differed from normal and hypertrophic scars. Normal and hypertrophic scars presented overlapping clustering, and eight genes were shown to be commonly expressed between hypertrophic and normal scars. No genes were specifically expressed at a higher level in keloid and normal scars. Based on gene ontology pathway analysis, genes with a higher level of expression in keloid scars lead to increased (extra-) cellular matrix proliferation and cell interaction. Moreover, tumour-like genes were more highly expressed in keloid scars, supporting the clinical impression of strong and diffuse growth. This study furthers our understanding of the classification of differential scar types based on molecular signature, which may shed light on new diagnostic and therapeutic strategies for keloid scars in the future.