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The Effect of microRNA-328 antagomir on erectile dysfunction in streptozotocin-induced diabetic rats
Dong-Shui Li1, Liang Feng1, Long-Hua Luo1
1Department of Andrology, The First Affiliated Hospital of Nangchang University, Nanchang 330006, PR China.
Abstract:
The study aimed at exploring the effect of microRNA-328 (miR-328) antagomir on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. A total of 120 male Sprague-Dawley (SD) rats were selected for this study. Fifteen rats were assigned as the diabetic control group and 75 out of the remaining rats (105 diabetic rat models) were divided into five groups with 15 rats in each group: diabetic ED, diabetic ED+negative control (NC), diabetic ED+miR-328 antagomir, diabetic ED+sildenafil and diabetic ED+miR-328 antagomir+sildenafil groups. The cGMP/AGEs production levels were measured using enzyme-linked immunosorbent assay (ELISA) test. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted for testing the expression level of miR-328, transcription and protein levels of endothelial nitric oxide synthase (eNOS) and dickkopf-3 (DKK3). The diabetic ED+miR-328 antagomir group had better erectile function, lower cGMP production level, transcription and protein levels of eNOS and DKK3 but higher AGEs production level than the diabetic control group. The diabetic control group showed higher cGMP production level transcription and protein levels of eNOS and DKK3 and lower production levels of AGEs and miR-328 than the diabetic ED and diabetic ED+NC groups. Our results indicated that miR-328 antagomir could improve ED in STZ-induced diabetic rats by regulating cGMP and AGEs.
Insights
MicroRNA-328 (miR-328) antagomir improved erectile dysfunction (ED) in diabetic rats. This therapy regulated cyclic guanosine monophosphate (cGMP) and advanced glycation end-products (AGEs), offering a potential treatment for diabetic ED.
Area of Science:
- Endocrinology
- Molecular Biology
- Urology
Background:
- Diabetic erectile dysfunction (ED) is a common complication of diabetes mellitus.
- MicroRNAs (miRNAs) play a role in the pathogenesis of diabetic complications, including ED.
- miR-328 has been implicated in regulating pathways relevant to ED.
Purpose of the Study:
- To investigate the therapeutic effect of microRNA-328 (miR-328) antagomir on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats.
- To explore the underlying mechanisms involving cyclic guanosine monophosphate (cGMP), advanced glycation end-products (AGEs), endothelial nitric oxide synthase (eNOS), and dickkopf-3 (DKK3).
Main Methods:
- Establishment of STZ-induced diabetic rat model for ED.
- Administration of miR-328 antagomir, sildenafil, or combinations.
- Measurement of cGMP and AGEs levels using ELISA.
- Assessment of miR-328 expression, eNOS, and DKK3 transcription (qRT-PCR) and protein levels (Western blotting).
Main Results:
- miR-328 antagomir treatment improved erectile function in diabetic rats.
- This improvement was associated with altered levels of cGMP, AGEs, eNOS, and DKK3.
- Specifically, miR-328 antagomir treatment led to lower cGMP, eNOS, and DKK3 levels, and higher AGEs levels compared to controls.
Conclusions:
- miR-328 antagomir demonstrates a therapeutic potential for improving diabetic ED.
- The mechanism involves the regulation of cGMP and AGEs pathways.
- Targeting miR-328 could be a novel strategy for managing erectile dysfunction in diabetic patients.
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