Deciphering Mesenchymal Drivers of Human Dupuytren’s Disease at Single-Cell Level

Abstract

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Proteomic Analysis of Dupuytren’s Contracture-Derived Sweat Glands Revealed the Synthesis of Connective Tissue Growth Factor and Initiation of Epithelial-Mesenchymal Transition as Major Pathogenetic Events

“…Nevertheless, also several non-structural ECM proteins such as mimecan, periostin, decorin and TGFBI were upregulated in DC associated sweat glands. Mimecan, periostin, decorin and TGFBI are proteins that have been shown to interact with fibrillar collagens, growth factors and growth factor receptors and thus influence ECM assembly, cellular growth, and migration [ 1 , 2 , 3 ]. TGFBI has been shown to be induced by TGF-β [ 34 ] and can affect heart and renal fibrosis [ 35 , 36 ].…”

“…Dupuytren’s contracture (DC) is a chronic and progressive fibroproliferative disorder restricted to the palmar fascia of the hands. A characteristic symptom of the late phase of the disease is the irreversible flexion contracture of one or more fingers with significant loss of their function [ 1 ]. The prevalence rates of this disease depend on the population group analyzed and are significantly higher in middle-aged or older men of Northern European descent [ 2 ].…”

“…High-throughput analyses of DC tissue have revealed valuable insight into the pathogenesis of this disease. Recent results from single-cell RNA sequencing outlined a population of podoplanin (PDPN)+ pathogenic fibroblasts, which were thought to drive the DC pathogenesis via several mechanisms that involved modulation of inflammation, extracellular matrix (ECM) deposition and cell proliferation [ 1 ]. Additionally, studying epigenetic and transcriptional profiles of primary human myofibroblasts obtained from DC nodules pointed to the acetyltransferase CREBBP/EP300 as an important regulator of contractility and ECM production through the control of H3K27 acetylation in the profibrotic genes, actin alpha 2, smooth muscle (ACTA2) and collagen type I (COL1A1) [ 6 ].…”

Fibroblast Activation Protein Targeted Photodynamic Therapy Selectively Kills Activated Skin Fibroblasts from Systemic Sclerosis Patients and Prevents Tissue Contraction

“…Unfortunately, no data has been reported on FAP expression in dermal fibroblasts in, e.g., dermatitis or systemic auto immune diseases with skin involvement such as systemic lupus erythematosus, psoriasis or arthritis psoriatica to support this idea. FAP positive fibroblasts have been identified in Dupuytren’s contracture, and the presence of myofibroblasts in this disease is associated with enhanced TNFα signaling [ 13 , 14 ].…”

Single-cell RNA sequencing reveals the heterogeneity of endothelial cells in human dupuytren’s disease

“…The pathogenesis of Dupuytren's disease remain largely unknown (Karbowiak et al 2021). Recent research using single-cell RNA sequencing (scRNA-seq) has expanded our understanding of the main cellular and molecular processes in mesenchymal cells that drive Dupuytren's disease (Dobie et al 2022). However, the involvement of other cells in developing Dupuytren's disease is largely unresolved.…”