The conserved molecular mechanism of erectile dysfunction in type 2 diabetes rats and mice by cross-species transcriptomic comparisons.

BACKGROUND

The poor clinical situation of type 2 diabetes-induced erectile dysfunction (T2DMED) creates an urgent need for new therapeutic targets.

AIM

To reveal the conserved molecular mechanism of T2DMED across species.

METHODS

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.

OUTCOMES

Cross-species transcriptomics of T2DMED rats and mice were analyzed and validated.

RESULTS

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.

CLINICAL IMPLICATIONS

To provide a new direction for improving the erectile ability of patients with T2DMED.

STRENGTHS AND LIMITATIONS

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.

CONCLUSIONS

Cross-species transcriptomic comparisons may offer a novel strategy for uncovering the underlying mechanisms and identifying therapeutic targets for T2DMED.