Liu, Cheng published the artcileDimethyl fumarate ameliorates stress urinary incontinence by reversing ECM remodeling via the Nrf2-TGF-β1/Smad3 pathway in mice., Quality Control of 624-49-7, the publication is International urogynecology journal (2022), 33(5), 1231-1242, database is MEDLINE.
INTRODUCTION AND HYPOTHESIS: Mechanical trauma and oxidative injury are involved in the pathogenesis of stress urinary incontinence (SUI), and oxidative stress (OS) is considered a potential therapeutic target. The antioxidant properties of dimethyl fumarate (DMF), a potent activator of Nrf2, have been highlighted recently. We therefore predicted that DMF might have therapeutic effects on mechanical trauma-induced SUI. METHODS: The SUI mice model was established by vaginal distension (VD). Leak point pressure (LPP), serum OS biomarkers, cell proliferation and apoptosis, collagen, elastin, matrix metalloproteinases (MMP), Nrf2, the TGF-β1/Smad3 signaling pathway, and the associated tissue growth factors in the anterior vaginal wall were measured in either wild-type or Nrf2-knockout (Nrf2–/–) female C57BL/6 mice. RESULTS: The results showed that DMF improved the VD-induced LPP reduction, alleviated oxidative injury, stimulated cell proliferation and inhibited apoptosis in the anterior vaginal wall tissue of mice. Moreover, DMF treatment reduced the hydrolysis of ECM proteins by MMP2 and MMP9. The above effects may be mediated by a series of tissue growth factors, including α-SMA, PAI-1, and TIMP-2, with the TGF-β1/Smad3 signaling pathway as the core regulatory mechanism. In further study, Nrf2–/– mice were used to replicate the SUI model. And the difference is that DMF failed to reactivate the TGF-β1/Smad3 pathway, nor did it improve LPP. CONCLUSIONS: Dimethyl fumarate can ameliorate urethra closure dysfunction in the VD-induced SUI mice model, and the therapeutic effect of DMF is mediated by the Nrf2-dominated antioxidant system and its downstream TGF-β1/Smad3 signaling pathway.
International urogynecology journal published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Quality Control of 624-49-7.
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