ArticleDiabetologia2020
Elevated pigment epithelium-derived factor induces diabetic erectile dysfunction via interruption of the Akt/Hsp90β/eNOS complex.
Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 14 citations in OpenAlex.
- Vascular aging-driven erectile dysfunction: pathophysiological mechanisms and emerging therapies-a narrative review.Translational andrology and urology · 2025Review
- Elevated PEDF promotes the occurrence of diabetes mellitus via suppressing GSIS by downregulating the SNARE complex.Communications biology · 2025Article
- Animal models in the study of diabetic erectile dysfunction: mechanisms and applications.Frontiers in endocrinology · 2025Review
- The role of microRNAs in erectile dysfunction: From pathogenesis to therapeutic potential.Frontiers in endocrinology · 2022Review
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisDiabetes mellitus erectile dysfunction (DMED) is a common complication of diabetes. The level of pigment epithelium-derived factor (PEDF) is significantly upregulated in the serum of individuals with obesity and diabetes. However, whether elevated PEDF levels contribute to DMED remains unknown. This study aimed to investigate the pathogenic role of PEDF and its related mechanism in DMED.
methodsWe enrolled 65 men, of whom 20 were nondiabetic control participants, 21 participants with diabetes but without erectile dysfunction, and 24 with DMED. The International Index of Erectile Function (IIEF-5) questionnaire was administered to evaluate erectile function. Plasma PEDF in diabetic participants and streptozotocin (STZ)-induced diabetic animals was detected by ELISA. Erectile function was evaluated by measuring the intracavernous pressure (ICP) and the ICP/mean arterial pressure (MAP) ratio in STZ-induced diabetic rats treated with PEDF-neutralising antibody (PEDF-Ab), db/db mice treated with PEDF-Ab, and Pedf knockout mice with STZ-induced diabetes. The overexpression of PEDF was implemented by intraperitoneal injection of recombinant PEDF and intracavernous injection of PEDF-expressing adenovirus. A mechanistic study was performed by immunofluorescence staining, bimolecular fluorescence complementation (BiFC), immunoprecipitation and western blotting.
resultsWe found that the plasma level of PEDF was significantly higher in participants with DMED compared with diabetic counterparts without erectile dysfunction and nondiabetic controls. Interestingly, PEDF levels were negatively correlated with plasma nitrite/nitrate levels and erectile function in DMED patients and STZ-induced diabetic rats. Furthermore, overexpression of PEDF significantly suppressed ICP and endothelial nitric oxide synthase (eNOS) phosphorylation in control rats. In contrast, the PEDF-Ab and Pedf knockout ameliorated ICP and eNOS phosphorylation in diabetic rats and mice. Mechanistically, PEDF promoted the membrane translocation of Hsp90β and directly bound to the amino acid residues 341-724 of Hsp90β on the endothelial cell surface, subsequently blocking intracellular Hsp90β/Akt/eNOS complex formation and downregulating eNOS phosphorylation. CONCLUSIONS/
interpretationThese results indicate that elevated PEDF levels contribute to impaired erectile function by suppressing Hsp90β-mediated eNOS phosphorylation and that PEDF may represent a novel therapeutic target for diabetic erectile dysfunction. Graphical abstract.
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