Aberrant connective tissue differentiation towards cartilage and bone underlies human keloids in African Americans. Issue 8 (28th February 2017)

• Record Type: Journal Article
• Authors: Fuentes‐Duculan, Judilyn; Bonifacio, Kathleen M.; Suárez‐Fariñas, Mayte; Kunjravia, Norma; Garcet, Sandra; Cruz, Tristan; Wang, Claire Q. F.; Xu, Hui; Gilleadeau, Patricia; Sullivan‐Whalen, Mary; Tirgan, Michael H.; Krueger, James G.
• Is Part Of: Experimental dermatology. Volume 26:Issue 8(2017)
• Page Start: 721
• Page End: 727
• Publication Date: 2017-02-28
• Subjects: cartilage and bone formation -- connective tissue differentiation -- keloid -- transcriptional profiling; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.13271
• Languages: English
• ISSNs: 0906-6705

Abstract

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 non‐lesional (NL) skin (n=3) and a newly formed keloid lesion using Affymetrix HGU133 2.0 plus arrays. Quantitative RT‐PCR (qRT‐PCR) and immunohistochemistry (IHC) staining were performed to confirm increased expression of relevant genes. We identified 1202 upregulated and 961 downregulated differentially expressed genes (DEGs) between keloid and NL skin; 1819 up‐ and 1867 downregulated DEGs between newly formed keloid and NL skin; and 492 up‐ and 775 downregulated DEGs between chronic and newly formed keloid (fold change >2, false discovery rate <0.05). Many of the top upregulated 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 alpha 1, Asporin (ASPN), Cadherin 11 (CDH11), Bone morphogenic protein 1 (BMP1), Secreted phosphoprotein 1 and Runt‐related transcription factor 2 (RUNX2). qRT‐PCR confirmed significant ( P <.05) upregulation of BMP1, RUNX2, CDH11 and FBN2 in chronic keloid compared to NL skin. IHC 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.