Defining a temporal gene expression profile of myofibroblast transformation in peyronie's disease

• Published in: Journal of sexual medicine Vol. 19; no. 11; p. S3
• Main Authors: Ilg, Marcus, Harding, Sophie, Lapthorn, Dr. Alice, Kirvell, Dr. Sara, Schurman, Nathan, Church, Sarah, Ralph, Prof. David, Bustin, Prof. Stephen, Cellek, Prof. Selim
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2022
• ISSN: 1743-6095; 1743-6109
• DOI: 10.1016/j.jsxm.2022.08.081

The transformation of fibroblasts to myofibroblasts is a key cellular event in the pathology of Peyronie's disease (PD). To date, gene expression changes have been analysed only at the start and end points of this process. This study aims to examine differences in temporal gene expression patterns at various other stages of myofibroblast transformation. Human primary fibroblasts were isolated from tunica albuginea (TA) of PD patients. Myofibroblast transformation was induced in these cells by exposure to 10 ng/mL Transforming Growth Factor-ß1 (TGF-ß1). RNA was isolated from cells before stimulation and 24, 36, 48, and 72 h after and analysed using the Nanostring nCounter Fibrosis Panel. 770 genes from 51 pathways were examined with a minimum raw expression threshold set to exclude artifacts. Genes with a >3-fold change were considered significant differential expression and further analysed. The top ten up- and down-regulated genes were confirmed by RT-qPCR. Out of 770 genes, 45 genes were differentially expressed with > 3-fold change in expression. 29 genes were up-regulated, and 16 genes were down-regulated. Altered gene expression patterns fell into three categories: those showing the strongest differential up- or down-regulation at 24h, at 72h or between 36h and 48h. Most changes in gene expression occurred within 24 hours and remained unchanged throughout the 72-hour period. Significant changes were observed in genes regulating inflammation, production and degradation of extracellular matrix proteins, chemoattraction, apoptosis, cell adhesion and proliferation. This study is the first to investigate the temporal expression of genes involved in myofibroblast transformation in PD. The three categories of genes identified might be responsible for different stages of the myofibroblast transformation process with those differentially expressed within 24h responsible for induction, those at 72h associated with maintenance of the myofibroblast phenotype, and those between 36h and 48h involved in a ‘point-of-no-return’ in myofibroblast transformation. None