Identification of fibrosis-related genes and biomarkers in diabetic erectile dysfunction.

BACKGROUND

Diabetic erectile dysfunction (DMED) has a high incidence and is poorly treated.

AIM

This study investigates fibrosis's genetic profiling and explores potential mechanisms for DMED.

METHODS

The DMED model was constructed in rats using streptozotocin. Erectile function was quantified using cavernous nerve electrostimulation. Fibrosis was evaluated using Masson's staining. RNA-seq was employed to analyze differentially expressed genes and fibrosis-related genes (FRGs) were acquired. Function enrichment analyses were performed, and genetic interaction was analyzed. Hub FRGs were screened using machine learning algorithms and Cytoscape tools and validated in Gene Expression Omnibus databases. Moreover, biological roles and subpopulation distribution of hub FRGs were determined.

OUTCOMES

Fibrosis-related genetic functions may play a vital role in DMED.

RESULTS

Based on comprehensive analysis, 45 differentially expressed FRGs were identified. These genes participate in regulating smooth muscle cell proliferation, vasoconstriction, and collagen-associated activities. Final analyses identified and validated a core gene signature comprising TIMP1, BMP7, and POSTN. They were closely associated with diabetic complications-related signaling pathways and extracellular matrix-receptor interaction.

CLINICAL TRANSLATION

The identified fibrosis-related gene signature may serve as the novel biomarkers for treating DMED.

STRENGTHS AND LIMITATIONS

The study is the first to investigate the genetic profiles behind fibrosis and DMED using comprehensive approaches. However, the validation is not adequate and more animal experiments are needed.

CONCLUSION

The gene profiling and biological functions of FRGs in DMED were identified. These results broaden the understanding of fibrosis in DMED.