Int Neurourol J.  2023 Dec;27(4):234-242. 10.5213/inj.2346074.037.

Differential Gene Expression in the Penile Cavernosum of Streptozotocin-Induced Diabetic Rats

Affiliations
  • 1Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University School of Medicine, Seoul, Korea
  • 2Department of Urology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University School of Medicine, Cheonan, Korea
  • 3Department of Biostatistics, Soonchunhyang University School of Medicine, Seoul, Korea
  • 4College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Korea
  • 5Research Institute, e-biogen Inc., Seoul, Korea

Abstract

Purpose
Men with diabetes mellitus (DM) often present with severe erectile dysfunction (ED). This ED is less responsive to current pharmacological therapies. If we know the upregulated or downregulated genes of diabetic ED, we can inhibit or enhance the expression of such genes through RNA or gene overexpression.
Methods
To investigate gene changes associated with ED in type 1 DM, we examined the alterations of gene expression in the cavernosum of streptozotocin-induced diabetic rats. Specifically, we considered 11,636 genes (9,623 upregulated and 2,013 downregulated) to be differentially expressed in the diabetic rat cavernosum group (n=4) compared to the control group (n=4). The analysis of differentially expressed genes using the gene ontology (GO) classification indicated that the following were enriched: downregulated genes such as cell cycle, extracellular matrix, glycosylphosphatidylinositol-anchor biosynthesis and upregulated genes such as calcium signaling, neurotrophin signaling, apoptosis, arginine and proline metabolism, gap junction, transforming growth factor-β signaling, tight junction, vascular smooth muscle contraction, and vascular endothelial growth factor (VEGF) signaling. We examined a more than 2-fold upregulated or downregulated change in expression, using real time polymerase chain reaction. Analysis of differentially expressed genes, using the GO classification, indicated the enrichment
Results
Of the 41,105 genes initially considered, statistical filtering of the array analysis showed 9,623 upregulated genes and 2,013 downregulated genes with at least 2-fold changes in expression (P<0.05). With Bonferroni correction, SLC2A9 (solute carrier family 2 member 9), LRRC20 (leucine rick repeat containing 20), PLK1 (polo like kinase 1), and AATK (apoptosis-associated tyrosine kinase) were all 2-fold changed genes.
Conclusions
This study broadens the scope of candidate genes that may be relevant to the pathophysiology of diabetic ED. In particular, their enhancement or inhibition could represent a novel treatment for diabetic ED.

Keyword

Diabetes; Erectile dysfunction; Gene
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