Aberrant connective tissue differentiation towards cartilage and bone underlies human keloids in African Americans

Abstract

Keloids are benign fibroproliferative tumors more frequently found among African Americans. Until now, keloid etiopathogenesis is not fully understood. To characterize keloids in African Americans, we performed transcriptional profiling of biopsies from large chronic keloids, adjacent nonlesional (NL) skin (n=3) and a newly formed keloid lesion using Affymetrix HGU133 2.0 plus arrays. Quantitative RT-PCR (qRT-PCR) and immunohistochemistry staining were done to confirm increased expression of relevant genes. We identified 1,202 up-regulated and 961 down-regulated differentially expressed genes (DEGs) between keloid and NL skin; 1,819 up- and 1,867 down-regulated DEGs between newly formed keloid and NL skin; and 492 up- and 775 down-regulated DEGs between chronic and newly formed keloid (Fold change >2, False discovery rate <0.05). Many of the top up-regulated DEGs between chronic keloid and NL skin, and between newly formed keloid and NL skin are involved in bone/cartilage formation including Fibrillin 2(FBN2), Collagen type X alpha1(COL10A1), Asporin(ASPN), Cadherin 11(CDH11), Bone morphogenic protein 1(BMP1), Secreted phosphoprotein 1(SPP1), and Runt-related transcription factor2(RUNX2). qRT-PCR confirmed significant (p<0.05) up-regulation of BMP1, RUNX2, CDH11 and FBN2 in chronic keloid compared to NL skin. Immunohistochemistry staining showed increased protein expression of ASPN, CDH11, BMP1 and RUNX2 on chronic and newly formed keloid compared to NL skin. Our study shows that large keloids in African Americans represent a dysplasia of cutaneous connective tissue towards immature cartilage or bone differentiation. The phenotype is potentially regulated by overexpression of RUNX2. This knowledge may give insights to guide the development of better treatment for the disease in the future.

This article is protected by copyright. All rights reserved.

http://ift.tt/2hrrgsv