Xiao Ming, Zeng Huanqing, Xu Yanghua, Xu Jiarong, Tan Xiaoli, Tang Yuxin
Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province 519000, China.
Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province 519000, China.
Sex Med. 2025 Mar 2;13(1):qfaf007. doi: 10.1093/sexmed/qfaf007. eCollection 2025 Feb.
The poor clinical situation of type 2 diabetes-induced erectile dysfunction (T2DMED) creates an urgent need for new therapeutic targets.
To reveal the conserved molecular mechanism of T2DMED across species.
T2DMED rat and mouse models were constructed to extract mRNA from corpus cavernosum for high-throughput sequencing. The differentially expressed genes (DEGs) were analyzed and the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Protein-Protein Interaction Networks were performed by bioinformatics methods. Immunohistochemistry, immunofluorescence, hematoxylin- eosin and Masson staining were used for subsequent verification.
Cross-species transcriptomics of T2DMED rats and mice were analyzed and validated.
Gene expression patterns in normal corpus cavernosum of mice and rats showed a strong correlation (r = 0.75, < 2.2 × 10), with a total of 15 691 homologous genes identified. In both species, 553 homologous down-regulated DEGs were identified, mainly enriched in pathways related to smooth muscle and mitochondrial functions, as revealed by KEGG and GO analyses. Immunohistochemistry and immunofluorescence confirmed the decreased expression of α-smooth muscle actin and in cavernosum tissues of T2DMED mice and rats. Additionally, 239 homologous up-regulated DEGs were identified, which were enriched in the signaling pathway and extracellular matrix composition. Subsequent experiments confirmed increased β-catenin expression and significant collagen accumulation, indicating fibrosis in T2DMED.
To provide a new direction for improving the erectile ability of patients with T2DMED.
The main strength is that cross-species transcriptomic sequencing has revealed the conserved molecular mechanisms of T2DMED. The main limitation is the lack of further validation in the T2DMED patients.
Cross-species transcriptomic comparisons may offer a novel strategy for uncovering the underlying mechanisms and identifying therapeutic targets for T2DMED.
2型糖尿病所致勃起功能障碍（T2DMED）的临床状况不佳，迫切需要新的治疗靶点。
揭示跨物种T2DMED的保守分子机制。
构建T2DMED大鼠和小鼠模型，从海绵体中提取mRNA进行高通量测序。分析差异表达基因（DEGs），并通过生物信息学方法进行京都基因与基因组百科全书（KEGG）、基因本体论（GO）和蛋白质-蛋白质相互作用网络分析。采用免疫组织化学、免疫荧光、苏木精-伊红和Masson染色进行后续验证。
对T2DMED大鼠和小鼠进行跨物种转录组学分析并验证。
小鼠和大鼠正常海绵体中的基因表达模式显示出很强的相关性（r = 0.75，< 2.2×10），共鉴定出15691个同源基因。在两个物种中，均鉴定出553个同源下调的DEGs，KEGG和GO分析显示，这些基因主要富集于与平滑肌和线粒体功能相关的通路。免疫组织化学和免疫荧光证实T2DMED小鼠和大鼠海绵体组织中α-平滑肌肌动蛋白表达降低。此外，鉴定出239个同源上调的DEGs，这些基因富集于Wnt信号通路和细胞外基质组成。后续实验证实β-连环蛋白表达增加和胶原显著积累，表明T2DMED存在纤维化。
为提高T2DMED患者的勃起能力提供新方向。
主要优点是跨物种转录组测序揭示了T2DMED的保守分子机制。主要局限性是缺乏在T2DMED患者中的进一步验证。
跨物种转录组比较可能为揭示T2DMED的潜在机制和确定治疗靶点提供一种新策略。
