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The transcriptomic analysis of bladder tissue in a rat model of ketamine-induced bladder fibrosis

ABSTRACT: The transcriptomic analysis of bladder tissue in a rat model of ketamine-induced bladder fibrosis

PROVIDER: PRJNA784574 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17066722.fastq.gz	Fastqsanger.gz
	SRR17066723.fastq.gz	Fastqsanger.gz
	SRR17066724.fastq.gz	Fastqsanger.gz
	SRR17066725.fastq.gz	Fastqsanger.gz
	SRR17066726.fastq.gz	Fastqsanger.gz

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The transcriptomic analysis of bladder tissue in a rat model of ketamine-induced bladder fibrosis

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Project description:Objective: Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. Methods: The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Results: Totally 3051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1414 up-regulated and 1637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression of five protein-encoding circRNA were further validated by quantitative RT-PCR and mass spectrometry. Conclusion: The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.

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Mesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder.

Project description:Abuse of the hallucinogenic drug ketamine promotes the development of lower urinary tract symptoms that resemble interstitial cystitis. The pathophysiology of ketamine-induced cystitis (KC) is largely unknown and effective therapies are lacking. Here, using a KC rat model, we show the therapeutic effects of human umbilical cord-blood (UCB)-derived mesenchymal stem cells (MSCs). Daily injection of ketamine to Sprague-Dawley rats for 2-weeks resulted in defective bladder function, indicated by irregular voiding frequency, increased maximum contraction pressure, and decreased intercontraction intervals and bladder capacity. KC bladders were characterized by severe mast-cell infiltration, tissue fibrosis, apoptosis, upregulation of transforming growth factor-? signaling related genes, and phosphorylation of Smad2 and Smad3 proteins. A single administration of MSCs (1?×?10(6)) into bladder tissue not only significantly ameliorated the aforementioned bladder voiding parameters, but also reversed the characteristic histological and gene-expression alterations of KC bladder. Treatment with the antifibrotic compound N-acetylcysteine also alleviated the symptoms and pathological characteristics of KC bladder, indicating that the antifibrotic capacity of MSC therapy underlies its benefits. Thus, this study for the first-time shows that MSC therapy might help to cure KC by protecting against tissue fibrosis in a KC animal model and provides a foundation for clinical trials of MSC therapy.

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