| Autor: |
Roth-Carter QR; Department of Pathology, and., Burks HE; Department of Pathology, and., Ren Z; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Koetsier JL; Department of Pathology, and., Tsoi LC; Department of Dermatology.; Department of Computational Medicine & Bioinformatics.; Department of Biostatistics, and., Harms PW; Department of Dermatology.; Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA., Xing X; Department of Dermatology., Kirma J; Department of Dermatology., Harmon RM; Department of Pathology, and., Godsel LM; Department of Pathology, and.; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Perl AL; Department of Pathology, and., Gudjonsson JE; Department of Dermatology., Green KJ; Department of Pathology, and.; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA. |
| Abstrakt: |
Darier, Hailey-Hailey, and Grover diseases are rare acantholytic skin diseases. While these diseases have different underlying causes, they share defects in cell-cell adhesion in the epidermis and desmosome organization. To better understand the underlying mechanisms leading to disease in these conditions, we performed RNA-seq on lesional skin samples from patients. The transcriptomic profiles of Darier, Hailey-Hailey, and Grover diseases were found to share a remarkable overlap, which did not extend to other common inflammatory skin diseases. Analysis of enriched pathways showed a shared increase in keratinocyte differentiation, and a decrease in cell adhesion and actin organization pathways in Darier, Hailey-Hailey, and Grover diseases. Direct comparison to atopic dermatitis and psoriasis showed that the downregulation in actin organization pathways was a unique feature in the acantholytic skin diseases. Furthermore, upstream regulator analysis suggested that a decrease in SRF/MRTF activity was responsible for the downregulation of actin organization pathways. Staining for MRTFA in lesional skin samples showed a decrease in nuclear MRTFA in patient skin compared with normal skin. These findings highlight the significant level of similarity in the transcriptome of Darier, Hailey-Hailey, and Grover diseases, and identify decreases in actin organization pathways as a unique signature present in these conditions. |
