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Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis.

ABSTRACT: 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.

SUBMITTER: Roth-Carter QR

PROVIDER: S-EPMC10543711 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis.

Roth-Carter Quinn R QR Burks Hope E HE Ren Ziyou Z Koetsier Jennifer L JL Tsoi Lam C LC Harms Paul W PW Xing Xianying X Kirma Joseph J Harmon Robert M RM Godsel Lisa M LM Perl Abbey L AL Gudjonsson Johann E JE Green Kathleen J KJ

JCI insight 20230822 16

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 e ...[more]

PMID: 37471166

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Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis.

Publications

Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis.

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