Gene expression profiling reveals alteration of caspase 6 and 14 transcripts in normal skin of keloid-prone patients

Nassiri, Mehdi; Woolery‐Lloyd, Heather; Ramos, Sharon; Jacob, Sharon E.; Gugic, Dijana; Viciana, Anita; Romanelli, Paolo; Elgart, George W.; Berman, Brian; Vincek, Vladimir

doi:10.1007/s00403-008-0880-z

Cited by 19 publications

(20 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we confirmed histopathologically that there was no fibrosis in the normal tissue, they may inherently contain abnormal characteristics. Indeed, another group 14 found differential expression of caspases 6 and 14 through an alternative approach to perform microarray analyses using normal skin from keloid-prone and from keloid-resistant individuals, although we did not detect any alteration in expression of those genes. Further, when comparing our results with their microarray analysis, also we found the up-regulation of mitogenactivated protein kinase 1.…”

Section: Discussioncontrasting

confidence: 70%

See 1 more Smart Citation

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

Inui

Shono

Nakajima

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

To elucidate pathogenic molecules in keloids, microarray analysis was performed using RNAs extracted from keloid-derived fibroblasts and normal skin-derived fibroblasts from the same patient with a typical keloid. Among 11 up-regulated extracellular matrix genes, cartilage oligomeric matrix protein (COMP) was most prominently increased. Up-regulation of COMP mRNA and protein was confirmed in the keloid tissue by quantitative RT-PCR and Western blot. Using immunohistochemistry, we compared 15 keloids and 6 control normal tissues using a COMPspecific antibody and found that COMP stained positively in 10 keloids (66.7%), whereas no staining was observed in normal tissues, demonstrating the ectopic expression of COMP in keloids. Comparing keloids smaller or larger than 10 cm 2 , the larger keloids were significantly more intensely stained with the COMP-specific antibody. Because COMP reportedly accelerates collagen type I fibril assembly, we examined whether extracellular type I collagen deposition is altered by silencing COMP mRNA by small interfering RNA (siRNA). Immunocytochemistry showed at 96 hours after transfection with COMP siRNA that the extracellular deposition of type I collagen was decreased compared to that observed with control siRNA. Further, COMP knockdown decreased amount collagens type I to V in the medium and on the cell surfaces. Our data suggest that COMP facilitates keloid formation by accelerating collagen deposition, thus providing a new therapeutic target.

show abstract

Section: Discussioncontrasting

confidence: 70%

“…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.…”

mentioning

confidence: 99%

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

Inui

Shono

Nakajima

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…93 qRT-PCR was used to determine gene expression levels in keloids. 91,94 Discrimination between collagen subtypes is often difficult to establish at the protein level because of the lack of specific antibodies. Therefore, changes in collagen synthesis are often assessed by qRT-PCR.…”

Section: Molecular Biological Methodsmentioning

confidence: 99%

“…Greco et al used this technique to compare skin gene expression levels between patients with burn wounds and normal skin samples, 90 and Nassiri et al investigated keloids with arrays specific for genes involved in apoptosis and cytokine signaling. 91 Microarrays are seen as an exploratory method to study differentially expressed genes in different RNA populations. In addition, qRT-PCR is often performed to confirm the differences detected with microarrays.…”

Section: Molecular Biological Methodsmentioning

confidence: 99%

An Overview of Methods for theIn VivoEvaluation of Tissue-Engineered Skin Constructs

Lammers

Verhaegen

Ulrich

et al. 2011

Tissue Engineering Part B: Reviews

View full text Add to dashboard Cite

Cutaneous wounding often leads to contraction and scarring, which may result in a range of functional, cosmetic, and psychological complications. Tissue-engineered skin substitutes are being developed to enhance restoration of the skin and improve the quality of wound healing. The aim of this review is to provide researchers in the field of tissue engineering an overview of the methods that are currently used to clinically evaluate skin wound healing, and methods that are used to evaluate tissue-engineered constructs in animal models. Clinically, the quality of wound healing is assessed by noninvasive subjective scar assessment scales and objective techniques to measure individual scar features. Alternatively, invasive technologies are used. In animal models, most tissue-engineered skin constructs studied are at least evaluated macroscopically and by using conventional histology (hematoxylin-eosin staining). Planimetry and immunohistochemistry are also often applied. An overview of antibodies used is provided. In addition, some studies used methods to assess gene expression levels and mRNA location, transillumination for blood vessel observation, in situ/in vivo imaging, electron microscopy, mechanical strength assessment, and microbiological sampling. A more systematic evaluation of tissue-engineered skin constructs in animal models is recommended to enhance the comparison of different constructs, thereby accelerating the trajectory to application in human patients. This would be further enhanced by the embracement of more clinically relevant objective evaluation methods. In addition, fundamental knowledge on construct-mediated wound healing may be increased by new developments in, for example, gene expression analysis and noninvasive imaging.

show abstract

“…Specifically, TGFβ and nerve growth factor expressions were significantly increased in keloid specimens compared with normal skin. 24 Another microarray study examining keloid specimens from patients of African or white ancestry demonstrated differences in caspase (apoptosis), cytokine, and mitogen-activated protein kinase pathways, 25 suggesting a genetic predisposition to keloid formation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Rapamycin-Treated Fibroblasts From Hypertrophic and Keloid Scars

Wong

You

Januszyk

et al. 2014

Annals of Plastic Surgery

View full text Add to dashboard Cite

Excess scar formation after cutaneous injury can result in hypertrophic scar (HTS) or keloid formation. Modern strategies to treat pathologic scarring represent nontargeted approaches that produce suboptimal results. Mammalian target of rapamycin (mTOR), a central mediator of inflammation, has been proposed as a novel target to block fibroproliferation. To examine its mechanism of action, we performed genomewide microarray on human fibroblasts (from normal skin, HTS, and keloid scars) treated with the mTOR inhibitor, rapamycin. Hypertrophic scar and keloid fibroblasts demonstrated overexpression of collagen I and III that was effectively abrogated with rapamycin. Blockade of mTOR specifically impaired fibroblast expression of the collagen biosynthesis genes PLOD, PCOLCE, and P4HA, targets significantly overexpressed in HTS and keloid scars. These data suggest that pathologic scarring can be abrogated via modulation of mTOR pathways in procollagen and collagen processing.

show abstract

Gene expression profiling reveals alteration of caspase 6 and 14 transcripts in normal skin of keloid-prone patients

Cited by 19 publications

References 25 publications

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

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

An Overview of Methods for theIn VivoEvaluation of Tissue-Engineered Skin Constructs

Transcriptional Profiling of Rapamycin-Treated Fibroblasts From Hypertrophic and Keloid Scars

Contact Info

Product

Resources

About