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A high-glucose diet aggravates experimental autoimmune prostatitis via DHVD3/VDR/ERK axis-mediated Th17 differentiation.

Created on 31 Jul 2026

Authors

Di Niu, Shao-Yu Yue, Xu Wang, Sheng-Ao Wei, Wei-Yi Li, Li Zhang, He-Xi Du, Chao-Zhao Liang

Published in

Asian journal of andrology. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent genitourinary disease that has gradually become recognized as a potential autoimmune disease. Our previous research revealed that a high-glucose diet exacerbated experimental autoimmune prostatitis (EAP), a widely used animal model of CP/CPPS. However, its effects on the metabolism of EAP mice remain unknown. Here, we applied non-targeted metabolomics analysis of feces and enzyme-linked immunosorbent assays to identify differential metabolites in EAP mice with and without high-glucose feeding. Metabolomics analysis demonstrated significant enrichment of the vitamin digestion and absorption pathway. Glucose-fed EAP mice exhibited increased fecal excretion and reduced absorption of 1,25-dihydroxyvitamin D3 (DHVD3) into the bloodstream, accompanied by decreased expression of the vitamin D receptor (VDR) in prostate tissue. In vitro experiments, proteomic sequencing, western blot, and flow cytometry analyses demonstrated that DHVD3 suppressed T helper 17 (Th17) cell differentiation by activating the VDR/extracellular signal-regulated kinase (ERK) pathway. DHVD3 supplementation ameliorated Th17 responses and EAP severity in glucose-fed mice, whereas the administration of the VDR antagonist MeTC7 reversed these effects. We concluded that high-glucose feeding aggravates EAP through DHVD3/VDR/ERK axis-mediated Th17 differentiation. VD3 supplementation may benefit CP/CPPS patients consuming a high-sugar diet.

PMID:
42535872
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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