RNA-sequencing profiling analysis of pericyte-derived extracellular vesicle\u2013mimetic nanovesicles-regulated genes in primary cultured fibroblasts from normal and Peyronie\u2019s disease penile tunica albuginea

Guo Nan Yin,Jiyeon Ock,Mi-Hye Kwon,Ji-Kan Ryu,Yong Song Gho,Lei Wang,Do-Kyun Kim,Shuguang Piao,Zhiyong Liu,Jun-Kyu Suh

doi:10.1186/s12894-021-00872-x

Abstract

BackgroundPeyronie’s disease (PD) is a severe fibrotic disease of the tunica albuginea that causes penis curvature and leads to penile pain, deformity, and erectile dysfunction. The role of pericytes in the pathogenesis of fibrosis has recently been determined. Extracellular vesicle (EV)–mimetic nanovesicles (NVs) have attracted attention regarding intercellular communication between cells in the field of fibrosis. However, the global gene expression of pericyte-derived EV–mimetic NVs (PC–NVs) in regulating fibrosis remains unknown. Here, we used RNA-sequencing technology to investigate the potential target genes regulated by PC–NVs in primary fibroblasts derived from human PD plaque.MethodsHuman primary fibroblasts derived from normal and PD patients was cultured and treated with cavernosum pericytes isolated extracellular vesicle (EV)–mimetic nanovesicles (NVs). A global gene expression RNA-sequencing assay was performed on normal fibroblasts, PD fibroblasts, and PD fibroblasts treated with PC–NVs. Reverse transcription polymerase chain reaction (RT-PCR) was used for sequencing data validation.ResultsA total of 4135 genes showed significantly differential expression in the normal fibroblasts, PD fibroblasts, and PD fibroblasts treated with PC–NVs. However, only 91 contra-regulated genes were detected among the three libraries. Furthermore, 20 contra-regulated genes were selected and 11 showed consistent changes in the RNA-sequencing assay, which were validated by RT-PCR.ConclusionThe gene expression profiling results suggested that these validated genes may be good targets for understanding potential mechanisms and conducting molecular studies into PD.

Highlights

Peyronie’s disease (PD) is a severe fibrotic disease of the tunica albuginea that causes penis curvature and leads to penile pain, deformity, and erectile dysfunction
We performed an RNA-sequencing assay on normal fibroblasts, PD fibroblasts, and PD fibroblasts treated with pericytederived Extracellular vesicles (EVs)–mimetic NVs (PC–NVs)
Transcriptional profiling and gene ontology (GO) category analysis For this study, three gene libraries for the normal fibroblast (NF), PD fibroblast (PF), and PC–NVs-treated PF (PFPC) groups were constructed for an RNA-sequencing assay (n = 4 for each group)

Summary

Introduction

Peyronie’s disease (PD) is a severe fibrotic disease of the tunica albuginea that causes penis curvature and leads to penile pain, deformity, and erectile dysfunction. Peyronie’s disease (PD) is caused by excessive fibrosis and scar tissue formation in the tunica albuginea (TA), resulting in penile pain, abnormal curvature, and erectile dysfunction (ED) [1, 2]. The most available medical therapy is collagenase and interferon injection and surgical intervention [3, 4] These treatments can cause glandular hypoesthesia and a high risk of new onset ED [5]. Recently studies have shown that the inhibition of angiogenesis may aggravate fibrosis [12, 13]. These findings suggest that different antiangiogenic and molecular targets produce different results in the treatment of fibrosis. We recently reported in a mouse model of diabetic ED that pericyte-derived angiogenic factor restored erectile function by enhancing cavernous angiogenesis [14, 15]

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