Dataset Information

Targeting the PRC2-dependent epigenetic program alleviates urinary tract infections.

ABSTRACT: Urinary tract infection (UTI) is a pervasive health problem worldwide. Patients with a history of UTIs suffer increased risk of recurrent infections, a major risk of antibiotic resistance. Here, we show that bladder infections induce expression of Ezh2 in bladder urothelial cells. Ezh2 is the methyltransferase of polycomb repressor complex 2 (PRC2)-a potent epigenetic regulator. Urothelium-specific inactivation of PRC2 results in reduced urine bacterial burden, muted inflammatory response, and decreased activity of the NF-κB signaling pathway. PRC2 inactivation also facilitates proper regeneration after urothelial damage from UTIs, by attenuating basal cell hyperplasia and increasing urothelial differentiation. In addition, treatment with Ezh2-specific small-molecule inhibitors improves outcomes of the chronic and severe bladder infections in mice. These findings collectively suggest that the PRC2-dependent epigenetic reprograming controls the amplitude of inflammation and severity of UTIs and that Ezh2 inhibitors may be a viable non-antibiotic strategy to manage chronic and severe UTIs.

SUBMITTER: Guo C

PROVIDER: S-EPMC10272480 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Targeting the PRC2-dependent epigenetic program alleviates urinary tract infections.

Guo Chunming C Zhao Mingyi M Sui Xinbing X Balsara Zarine Z Zhai Songhui S Ahdoot Michael M Zhang Yingsheng Y Lam Christa M CM Zhu Ping P Li Xue X

iScience 20230520 6

Urinary tract infection (UTI) is a pervasive health problem worldwide. Patients with a history of UTIs suffer increased risk of recurrent infections, a major risk of antibiotic resistance. Here, we show that bladder infections induce expression of <i>Ezh2</i> in bladder urothelial cells. <i>Ezh2</i> is the methyltransferase of polycomb repressor complex 2 (PRC2)-a potent epigenetic regulator. Urothelium-specific inactivation of PRC2 results in reduced urine bacterial burden, muted inflammatory r ...[more]

PMID: 37332606

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Project description:BackgroundCranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections. The aim of this review is to assess the effectiveness of cranberries in treating such infections.ObjectivesTo assess the effectiveness of cranberries for the treatment of urinary tract infections.Search strategyThe search strategy developed by the Cochrane Renal Group was used. Also, companies involved with the promotion and distribution of cranberry preparations were contacted; electronic databases and the Internet were searched using English and non English language terms; reference lists of review articles and relevant trials were also searched.Selection criteriaAll randomised or quasi randomised controlled trials of cranberry juice or cranberry products for the treatment of urinary tract infections. Trials of men, women or children were included.Data collection and analysisTitles and abstracts of studies that were potentially relevant to the review were screened by one reviewer, RJ, who discarded studies that were clearly ineligible but aimed to be overly inclusive rather than risk losing relevant studies. Reviewers RJ and LM independently assessed whether the studies met the inclusion criteria. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility.Main resultsNo trials were found which fulfilled all of the inclusion criteria. Two trials were excluded because they did not have any relevant outcomes.Reviewer's conclusionsAfter a thorough search, no randomised trials which assessed the effectiveness of cranberry juice for the treatment of urinary tract infections were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of urinary tract infections. Well-designed parallel group, double blind trials comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating urinary tract infections are needed. Outcomes should include reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. Dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these trials.

Dataset Information

Targeting the PRC2-dependent epigenetic program alleviates urinary tract infections.

Publications

Targeting the PRC2-dependent epigenetic program alleviates urinary tract infections.

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