Human Urine-Derived Stem Cells Improve Partial Bladder Outlet Obstruction in Rats: Preliminary Data and microRNA-mRNA Expression Profile

Stem Cell Reviews and Reports - Tập 18 Số 7 - Trang 2403-2413 - 2022
Menjiang Tu1, Rui Wang1, Ping Zhu1, Qingqing Wang2, Bishao Sun2, Keshi Lu1, Jiawei Zhang1, Weihua Xie1, Huan Guo1, Shulin Li1, Yuqi Wu1, Xiangwei Wang1
1Department of Urology, Southern University of Science and Technology Hospital, Liuxian Street, Nanshan District, Shenzhen, NO.6019, China
2Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China

Tóm tắt

AbstractPartial bladder outlet obstruction (pBOO) often results in bladder tissue inflammation and remodeling. As human urine-derived stem cells (USCs) have demonstrated therapeutic benefits, we used a rat model to investigate the effect of USCs on bladder function and explore the miRNA and gene expression profiles in bladder tissue using RNA sequencing. Eighteen rats were assigned to a sham surgery group, pBOO group, and pBOO+USC group (six biweekly treatments). Routine urodynamic monitoring, analysis of detrusor muscle strips, and pathophysiology assessments were conducted. Finally, altered miRNA and mRNA expression profiles of bladder tissue were examined using RNA sequencing and bioinformatics analysis. After USC treatment, elevated bladder compliance and maximal voiding pressure, declined end filling pressure and voided volume, and improved detrusor muscle contractility and carbachol sensitivity were found. Histology and TUNEL assay revealed reduced collagen deposition and muscle cell apoptosis in bladder tissue. The differential expression of eight miRNAs was reversed by USC treatment. Two large nodes (miR-142 and miR-9a) were identified in the miRNA-gene interaction network in the USC-treated group. The Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment of multiple significant pathways, including those involved in necroptosis and cytokine-cytokine receptor interactions. This is the first study to demonstrate the protective effect of USCs on bladder function and remodeling in pBOO rats. The miRNA and mRNA expression levels differed in the bladder of pBOO rats with and without USC treatment. Although the mechanism underlying these effects has not been fully elucidated, necroptosis and cytokine-cytokine receptor interaction-related pathways may be involved. Graphical abstract

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Tài liệu tham khảo

Jiang, Y. H., Lee, C. L., & Kuo, H. C. (2016). Urothelial dysfunction, suburothelial inflammation and altered sensory protein expression in men with bladder outlet obstruction and various bladder dysfunctions: Correlation with urodynamics. Journal of Urology, 196(3), 831–837.

Wiafe, B., Adesida, A. B., Churchill, T., Kadam, R., Carleton, J., & Metcalfe, P. D. (2019). Mesenchymal stem cell therapy inhibited inflammatory and profibrotic pathways induced by partial bladder outlet obstruction and prevented high-pressure urine storage. Journal of Pediatric Urology, 15(3), 254.e1–254.e10.

Oka, M., Fukui, T., Ueda, M., Tagaya, M., Oyama, T., & Tanaka, M. (2009). Suppression of bladder oxidative stress and inflammation by a phytotherapeutic agent in a rat model of partial bladder outlet obstruction. Journal of Urology, 182(1), 382–390.

Wang, Q., Zhao, J., Wu, C., Yang, Z., Dong, X., Liu, Q., et al. (2017). Large conductance voltage and Ca(2+)-activated K(+) channels affect the physiological characteristics of human urine-derived stem cells. American Journal of Translational Research, 9(4), 1876–1885.

Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009). Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biology, 10(3), R25.

Friedländer, M. R., Mackowiak, S. D., Li, N., Chen, W., & Rajewsky, N. (2012). miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucleic Acids Research, 40(1), 37–52.

Enright, A. J., John, B., Gaul, U., Tuschl, T., Sander, C., & Marks, D. S. (2003). MicroRNA targets in Drosophila. Genome Biology, 5(1), R1.

Malkowicz, S. B., Wein, A. J., Elbadawi, A., Van Arsdalen, K., Ruggieri, M. R., & Levin, R. M. (1986). Acute biochemical and functional alterations in the partially obstructed rabbit urinary bladder. Journal of Urology, 136(6), 1324–1329.

Yuan, X., Wu, S., Lin, T., He, D., Li, X., Liu, S., et al. (2011). Role of nitric oxide synthase in bladder pathologic remodeling and dysfunction resulting from partial outlet obstruction. Urology, 77(1008), e1–e8.

Zeng, J., Xie, K., Jiang, C., Mo, J., & Lindström, S. (2012). Bladder mechanoreceptor changes after artificial bladder outlet obstruction in the anesthetized rat. Neurourology and Urodynamics, 31(1), 178–184.

Austin, J. C., Chacko, S. K., DiSanto, M., Canning, D. A., & Zderic, S. A. (2004). A male murine model of partial bladder outlet obstruction reveals changes in detrusor morphology, contractility and myosin isoform expression. Journal of Urology, 172(4 Part 1), 1524–1528.

Al-Saikan, B., Ding, J., Tredget, E., & Metcalfe, P. (2016). Benefits of mesenchymal stem cells after partial bladder outlet obstruction. Canadian Urological Association Journal, 10(1–2), E1–E6.

Woo, L. L., Tanaka, S. T., Anumanthan, G., Pope, J. C., Thomas, J. C., Adams, M. C., et al. (2011). Mesenchymal stem cell recruitment and improved bladder function after bladder outlet obstruction: Preliminary data. Journal of Urology, 185(3), 1132–1138.

Wiafe, B., Adesida, A., Churchill, T., & Metcalfe, P. (2018). Mesenchymal stem cells inhibit hypoxia-induced inflammatory and fibrotic pathways in bladder smooth muscle cells. World Journal of Urology, 36(7), 1157–1165.

Sun, B., Luo, X., Yang, C., Liu, P., Yang, Y., Dong, X., et al. (2019). Therapeutic effects of human urine-derived stem cells in a rat model of cisplatin-induced acute kidney injury in vivo and in vitro. Stem Cells International, 2019, 8035076.

Zhang, C., George, S. K., Wu, R., Thakker, P. U., Abolbashari, M., Kim, T. H., et al. (2020). Reno-protection of urine-derived stem cells in a chronic kidney disease rat model induced by renal ischemia and nephrotoxicity. International Journal of Biological Sciences, 16(3), 435–446.

Ouyang, B., Xie, Y., Zhang, C., Deng, C., Lv, L., Yao, J., et al. (2019). Extracellular vesicles from human urine-derived stem cells ameliorate erectile dysfunction in a diabetic rat model by delivering proangiogenic microRNA. Sexual Medicine, 7(2), 241–250.

Ling, X., Zhang, G., Xia, Y., Zhu, Q., Zhang, J., Li, Q., et al. (2020). Exosomes from human urine-derived stem cells enhanced neurogenesis via miR-26a/HDAC6 axis after ischaemic stroke. Journal of Cellular and Molecular Medicine, 24(1), 640–654.

Dong, X., Zhang, T., Liu, Q., Zhu, J., Zhao, J., Li, J., et al. (2016). Beneficial effects of urine-derived stem cells on fibrosis and apoptosis of myocardial, glomerular and bladder cells. Molecular and Cellular Endocrinology, 427, 21–32.

Chen, C. Y., Rao, S. S., Ren, L., Hu, X. K., Tan, Y. J., Hu, Y., et al. (2018). Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics, 8(6), 1607–1623.

Li, X., Liao, J., Su, X., Li, W., Bi, Z., Wang, J., et al. (2020). Human urine-derived stem cells protect against renal ischemia/reperfusion injury in a rat model via exosomal miR-146a-5p which targets IRAK1. Theranostics, 10(21), 9561–9578.

Gheinani, A. H., Köck, I., Vasquez, E., Baumgartner, U., Bigger-Allen, A., Sack, B. S., et al. (2018). Concordant miRNA and mRNA expression profiles in humans and mice with bladder outlet obstruction. American Journal of Clinical and Experimental Urology, 6(6), 219–233.

Gheinani, A. H., Kiss, B., Moltzahn, F., Keller, I., Bruggmann, R., Rehrauer, H., et al. (2017). Characterization of miRNA-regulated networks, hubs of signaling, and biomarkers in obstruction-induced bladder dysfunction. JCI Insight, 2(2), e89560.

Iguchi, N., Hou, A., Koul, H. K., & Wilcox, D. T. (2014). Partial bladder outlet obstruction in mice may cause E-cadherin repression through hypoxia induced pathway. Journal of Urology, 192(3), 964–972.

Sharma, S., Liu, J., Wei, J., Yuan, H., Zhang, T., & Bishopric, N. H. (2012). Repression of miR-142 by p300 and MAPK is required for survival signalling via gp130 during adaptive hypertrophy. EMBO Molecular Medicine, 4(7), 617–632.

Su, S., Zhao, Q., He, C., Huang, D., Liu, J., Chen, F. et al. (2015). miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program. Nature Communications, 6, 8523.

Cao, Y., Zhang, H., Lu, X., Wang, J., Zhang, X., Sun, S., et al. (2020). Overexpression of microRNA-9a-5p ameliorates NLRP1 inflammasome-mediated ischemic injury in rats following ischemic stroke. Neuroscience, 444, 106–117.

Yang, D., Yu, J., Liu, H. B., Yan, X. Q., Hu, J., Yu, Y., et al. (2019). The long non-coding RNA TUG1-miR-9a-5p axis contributes to ischemic injuries by promoting cardiomyocyte apoptosis via targeting KLF5. Cell Death and Disease, 10(12), 908.

Qi, F., Hu, J. F., Liu, B. H., Wu, C. Q., Yu, H. Y., Yao, D. K., et al. (2015). MiR-9a-5p regulates proliferation and migration of hepatic stellate cells under pressure through inhibition of Sirt1. World Journal of Gastroenterology, 21(34), 9900–9915.

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Stem Cell Reviews and Reports

Tập 18 Số 7

2403-2413

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