Mp66-05 the Role and Mechanism of Macrophage Induced Fibroblast-to-Myofibroblast Transition in Diabetic Penile Cavernous Fibrosis

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP66)1 May 2024MP66-05 THE ROLE AND MECHANISM OF MACROPHAGE INDUCED FIBROBLAST-TO-MYOFIBROBLAST TRANSITION IN DIABETIC PENILE CAVERNOUS FIBROSIS Huirong Chen Huirong ChenHuirong Chen View All Author Informationhttps://doi.org/10.1097/01.JU.0001009468.01097.19.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The prevalence rate of diabetes mellitus induced erectile dysfunction (DMED) is high, which seriously affected men's physical and mental health. Corpora cavernous fibrosis is an important cause of poor medical efficacy for DMED, and its mechanism has not been fully elucidated. Studies have shown that macrophages regulate fibroblast-to-myofibroblast transition, which is associated with fibrosis. The purpose of this study was to investigate the role and mechanism of macrophages in the fibroblast-to-myofibroblast transition in diabetic penile cavernous fibrosis. METHODS: scRNA-seq was used to map the single cell transcription of human penile cavernosum tissues, including 2 males with normal erectile function, 3 DMED and 2 non-DMED patients. Macrophages were labeled with CD163, and M1 and M2 macrophage were labeled with CD86 and CD206, respectively, and the expression of pro-inflammatory and anti-inflammatory/pro-fibrotic factors secreted by macrophages was analyzed. Cellular communication of TGF-β1 between cell subpopulations was analyzed. RESULTS: Seven subpopulations of penile sponge cells were identified, including VWF (endothelial cells), PDGFRA (fibroblasts), KCNJ8 (pericytes), ACTA2 (smooth muscle cells), S100B (Schwann cells), CD163 (macrophages), and CD3E (T cells). Compared with normal, the proliferation of APOC1+ fibroblast subpopulation increased in DMED, suggesting that the number of myoid cells in fibroblast subpopulation increased in DMED. Type IV collagen gene expression increased, type I and type VI collagen gene expression decreased, indicating that unbalanced collagen deposition were showed in DMED. M2 macrophages increased, M1 macrophages decreased, and M2/M1 ratio increased in DMED. In DMED, the expression of TGF-β1 mRNA increased in macrophages, decreased in fibroblast cells. The expression of pro-inflammatory factors (TNF-α, IL-1B, MMP9) and anti-inflammatory/pro-fibrotic factors (IL10, FGF5, PDGFB) were increased in macrophage. Cell communication analysis of TGF-β1 between seven cell subpopulations revealed enhanced TGF-β1 communication between fibroblast and macrophages. CONCLUSIONS: The increase of myoid cells and unbalanced collagen deposition in fibroblasts suggested that fibroblasts showed the characteristics of fibroblast-to-myofibroblast transition in DMED. In the persistent state of diabetes, the M2/M1 ratio of corpus cavernosum increases, the M2 macrophages release TGF-β1, paracrine acts on fibroblasts to induce fibroblast-to-myofibroblast transition, and thus lead to corpus cavernosum fibrosis. In addition, the increased release of FGF5 and PDGFB by macrophages may also participate in the process of corpus cavernosum fibrosis in DMED. Source of Funding: No © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1087 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Huirong Chen More articles by this author Expand All Advertisement PDF downloadLoading ...