Extracellular Matrix and Protein Phosphorylation Dysregulation Related to Diabetes-Induced Erectile Dysfunction

Abstract

Diabetes can cause erectile dysfunction (ED) in more than half of male patients. However, the mechanisms underlying diabetes-induced erectile dysfunction (DED) remain unknown. This study is aimed at systematically analyzing the cellular and molecular mechanisms leading to DED using bioinformatic analysis and providing molecular targets for predicting and treating DED. In total, we identified 800 DEGs in the DED samples compared with those in the control group. The 407 upregulated DEGs were mainly enriched in glucose and lipid metabolism-related pathways, and the 393 downregulated DEGs were primarily enriched in tissue development and structure. Dysregulated extracellular matrix genes (especially collagen and elastin) may be closely related to damage to the erectile function of the corpus cavernosum. Sixteen hub genes and 24 modules were detected with hub genes and MCODE analysis. The consensus sequence AAA (G/C) AAA was observed at the promoter sites of most genes that were enriched in the “posttranslational protein phosphorylation” pathway. These genes had abundant phosphorylation sites. Furthermore, 20 TFs targeting DEGs were identified using ChEA3 tool. In conclusion, our research comprehensively and systematically describes the molecular characteristics of DED and suggests that dysregulated extracellular matrix genes and protein phosphorylation may play critical roles in DED. Therefore, they may be potential markers for diagnosing and treating DED.