Involvement of TL1A and DR3 in induction of ischaemia and inflammation in urinary bladder dysfunction in the elderly

Wang,Wei; Zhang,Ning; Zhu,Xu-Hui; He,Zhi-Song; Wahafu,Wasilijiang; Xu,Zhi-Qing; Yang,Yong

doi:10.3892/mmr.2012.928

Involvement of TL1A and DR3 in induction of ischaemia and inflammation in urinary bladder dysfunction in the elderly

Authors:
- Wei Wang
- Ning Zhang
- Xu-Hui Zhu
- Zhi-Song He
- Wasilijiang Wahafu
- Zhi-Qing Xu
- Yong Yang
View Affiliations

Affiliations: Urology Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China, Department of Urology, Peking University First Hospital, The Institute of Urology, Peking University, Beijing 100034, P.R. China, Beijing Institute of Neuroscience, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing 100069, P.R. China
Published online on: May 25, 2012 https://doi.org/10.3892/mmr.2012.928
Pages: 434-438

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Benign prostatic hyperplasia often causes intravesical obstruction in elderly men; however, the processes of aging and bladder outlet obstruction independently evoke alterations in the structure and function of the bladder. These changes lead to lower urinary tract symptoms; however, it is difficult to separate the effects of prostatic obstruction on the bladder from those of aging. Nevertheless, few studies have focused on elucidating the pathophysiological mechanisms in the aged bladder. Bladder dysfunction due to detrusor instabitliy (caused by old age) is considered to be associated with chronic ischaemia and inflammation. The aim of this study was to explore the role of tumour necrosis factor (TNF)-like ligand 1A (TL1A) and death-domain receptor (DR)3 in the ischaemic and inflammatory process of aged bladder dysfunction. Sixteen bladder tissue samples collected from patients with urothelial tumours of the bladder were divided into two groups according to age: group 1 (controls, n=8) and group 2 (aged group, n=8). Urodynamic examinations were preformed before radical cystectomy. The full-thickness bladder tissues were obtained at least 5 cm away from the margin of the tumours. The mRNA expression levels of TL1A, DR3, von Willebrand factor (vWF), interleukin (IL)-6 and nerve growth factor (NGF) in the two groups were determined using real-time reverse transcription-PCR and the protein expression levels of TL1A, DR3 and p65 were determined by western blot analysis. The TL1A and DR3 mRNA and protein expression levels of the aged bladders were upregulated compared to the control group (p<0.05). Compared to the control, the mRNA expression levels of vWF in the aged bladder tissues were markedly lower (p<0.01); however, the mRNA expression levels of IL-6 were significantly higher in the aged bladder tissues (p<0.01) compared to the control. No significant difference in NGF mRNA expression between the two groups was detected (p>0.05). In conclusion, the aged bladder was associated with ischaemic and inflammatory alterations in comparison to the control group. TL1A and DR3 may play an important role in the pathophysiological process of the aged bladder.

View Figures

View References

1	Madersbacher S, Pycha A, Schatzl G, Mian C, Klingler CH and Marberger M: The aging lower urinary tract: a comparative urodynamic study of men and women. Urology. 51:206–212. 1998.
2	Taylor JA III and Kuchel GA: Detrusor underactivity: clinical features and pathogenesis of an underdiagnosed geriatric condition. J Am Geriatr Soc. 54:1920–1932. 2006.
3	Azadzoi KM, Tarcan T, Siroky MB and Krane RJ: Atherosclerosis-induced chronic ischaemia causes bladder fibrosis and non-compliance in the rabbit. J Urol. 161:1626–1635. 1999.
4	Azadzoi KM, Radisavljevic ZM, Golabek T, Yalla SV and Siroky MB: Oxidative modification of mitochondrial integrity and nerve fiber density in the ischaemic overactive bladder. J Urol. 83:362–369. 2010.
5	Azadzoi KM, Tarcan T, Kozlowski R, Krane RJ and Siroky MB: Overactivity and structural changes in the chronically ischaemic bladder. J Urol. 162:1768–1778. 1999.
6	Azadzoi KM, Shinde VM, Tarcan T, Kozlowski R and Siroky MB: Increased leukotriene and prostaglandin release, and overactivity in the chronically ischaemic bladder. J Urol. 169:1885–1891. 2003.
7	Migone TS, Zhang J, Luo X, et al: TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Immunity. 16:479–492. 2002.
8	Kang YJ, Kim WJ, Bae HU, et al: Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis. Cytokine. 29:229–235. 2005.
9	Zhai Y, Yu J, Iruela-Arispe L, et al: Inhibition of angiogenesis and breast cancer xenograft tumour growth by VEGI, a novel cytokine of the TNF superfamily. Int J Cancer. 82:131–136. 1999.
10	Zhang N, Sanders AJ, Ye L, Kynaston HG and Jiang WG: Expression of vascular endothelial growth inhibitor (VEGI) in human urothelial cancer of the bladder and its effects on the adhesion and migration of bladder cancer cells in vitro. Anticancer Res. 30:87–95. 2010.
11	Al-Lamki RS, Wang J, Tolkovsky AM, et al: TL1A both promotes and protects from renal inflammation and injury. J Am Soc Nephrol. 19:953–960. 2008.
12	Takedatsu H, Michelsen KS, Wei B, et al: TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology. 135:552–567. 2008.
13	Bamias G, Martin C III, Marini M, et al: Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. J Immunol. 171:4868–4874. 2003.
14	Zhang J, Wang X, Fahmi H, et al: Role of TL1A in the pathogenesis of rheumatoid arthritis. J Immunol. 183:5350–5357. 2009.
15	Abrams P, Blaivas JG, Stanton SL and Andersen JT: The standardisation of terminology of lower urinary tract function. The International Continence Society Committee on Standardisation of Terminology. Scand J Urol Nephrol Suppl. 114:5–19. 1988.
16	Azadzoi KM, Yalla SV and Siroky MB: Oxidative stress and neurodegeneration in the ischaemic overactive bladder. J Urol. 178:710–715. 2007.
17	Poncelet C, Madelenat P, Feldmann G, Walker F and Darai E: Expression of von Willebrand’s factor, CD34, CD31, and vascular endothelial growth factor in uterine leiomyomas. Fertil Steril. 78:581–586. 2002.
18	Jahroudi N and Lynch DC: Endothelial-cell-specific regulation of von Willebrand factor gene expression. Mol Cell Biol. 14:999–1008. 1994.
19	Tian F, Liang PH and Li LY: Inhibition of endothelial progenitor cell differentiation by VEGI. Blood. 113:5352–5360. 2009.
20	Chew LJ, Pan H, Yu J, et al: A novel secreted splice variant of vascular endothelial cell growth inhibitor. FASEB J. 16:742–744. 2002.
21	Lachtermacher S, Esporcatte BL, Montalvao F, et al: Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischaemic heart failure. Braz J Med Biol Res. 43:377–389. 2010.
22	Shih DQ, Kwan LY, Chavez V, et al: Microbial induction of inflammatory bowel disease associated gene TL1A (TNFSF15) in antigen presenting cells. Eur J Immunol. 39:3239–3250. 2009.
23	Gu Q, Yang XP, Bonde P, DiPaula A, Fox-Talbot K and Becker LC: Inhibition of TNF-alpha reduces myocardial injury and proinflammatory pathways following ischaemia-reperfusion in the dog. J Cardiovasc Pharmacol. 48:320–328. 2006.
24	Phillips JI: Inflammatory plasma cell infiltration of the urinary bladder in the aging C57BL/Icrfa(t) mouse. Invest Urol. 19:75–78. 1981.
25	Wen L, Zhuang L, Luo X and Wei P: TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells. J Biol Chem. 278:39251–39258. 2003.
26	Haferkamp A, Dorsam J, Resnick NM, Yalla SV and Elbadawi A: Structural basis of neurogenic bladder dysfunction. III Intrinsic detrusor innervation. J Urol. 169:555–562. 2003.
27	Karamoysoyli E, Burnand RC, Tomlinson DR and Gardiner NJ: Neuritin mediates nerve growth factor-induced axonal regeneration and is deficient in experimental diabetic neuropathy. Diabetes. 57:181–189. 2008.
28	Yang JP, Liu HJ, Yang H and Feng PY: Therapeutic time window for the neuroprotective effects of NGF when administered after focal cerebral ischaemia. Neurol Sci. 32:433–441. 2011.
29	Lowe EM, Anand P, Terenghi G, Williams-Chestnut RE, Sinicropi DV and Osborne JL: Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br J Urol. 79:572–577. 1997.
30	Birder LA, Wolf-Johnston A, Griffiths D and Resnick NM: Role of urothelial nerve growth factor in human bladder function. Neurourol Urodyn. 26:405–409. 2007.