Identification of unique gene expression patterns within different lesional sites of keloids

Abstract

Keloid disease is a significant clinical problem, especially in black populations, with an estimated incidence of 4-16%. Keloids are fibroproliferative dermal tumors developing as a result of deregulated wound healing. The dynamic nature of keloids is illustrated by clinical regression in the center, while the margin remains active growing into the surrounding healthy skin. Therefore, the gene expression profiles of fibroblasts from different sites of the keloids were characterized using Affymetrix microarrays covering the whole human genome. This study revealed 105 genes that were differentially regulated (79 genes were up-regulated and 26 down-regulated) in a unique gene expression profile in different sites of keloids where progression or regression of the process was in progress. The apoptosis inhibitor AVEN was found to be up-regulated at the active margin of keloids, while apoptosis-inducing genes such as ADAM12 and genes inducing extracellular matrix (ECM) degradation such as matrix metalloproteinase-19 were up-regulated in the regressing keloid center. We identified genes previously not described in the development of keloids. Activating proapoptotic genes or inhibiting ECM-inducing genes as INHBA or monocyte chemoattractant protein-1 might be possible target genes for new treatment strategies for keloid disease.

Identification and Characterization of Cartilage Oligomeric Matrix Protein as a Novel Pathogenic Factor in Keloids

“…Indeed, the previous microarrays, which compared keloid tissues or fibroblasts with normal tissues or NDFs from nonkeloid different persons, 13,15,16 could show the difference of collagen type I expression. However, when using KDFs and NDFs from the same keloid patient 43 or KDFs and normal scar derived fibroblasts, 9 the microarrays could not detect any significant difference of collagen type I expression.…”

“…To explore novel target molecules, microarray analyses of keloids have been performed and reported the up-regulated expression of many genes related to the cell cycle, 13 intercellular signaling 14 and the extracellular matrix, 9,15,16 and the down-regulated expression apoptosis-related genes.…”

Effect of Collagen Nanotopography on Keloid Fibroblast Proliferation and Matrix Synthesis: Implications for Dermal Wound Healing

“…The orientation of cutting the specimens with respect to epithelial surface was inconsistent between the studies, that is, perpendicular, 7 parallel and perpendicular, 9,10 or oblique, 11 or the details of routine procedures were not clarified, 8,10 which may interfere with interpretation of the data. The fact that the keloid scar has a regressing center and growing margins, 5,6 each with a possibly different collagen architecture, could further complicate the comparison.…”

“…At the center of the scar, cells reside on a matrix of aligned collagen fibrils 7 and show decreased proliferation; 5,6 whereas at the active margin, cells encounter a random network of collagen fibrils as seen in normal skin 7 and exhibit higher rates of proliferation. 5,6 Not only is the rate of proliferation very different in the two regions of the keloid, but also there is a difference in collagen fibril organization, suggesting a correlation between collagen architecture and keloid growth.…”

“…4 The aggressive nature of a keloid is demonstrated by the fact that the center of the keloid is in clinical regression, and it has a reduced rate of cell proliferation, while fibroblasts in the growing margin are highly proliferative and often invade the surrounding healthy tissue. 5,6 Collagen arrangement in keloid scar tissue differs from those in normal skin and in both normal and hypertrophic scar tissues. 7 Healthy skin has a three-dimensional basketweave-like network of distinct collagen bundles, each formed by a parallel array of closely packed collagen fibrils.…”