Does urokinase play a role in renal stone formation?

Mammalian bladder epithelium functions as an effective permeability barrier. We demonstrate here that this epithelium can also function as a secretory tissue directly involved in modifying urinary protein composition. Our data indicate that normal bovine urothelium synthesizes, as its major differentiation products, two wellknown proteases: tissue-type plasminogen activator and urokinase, as well as a serine protease inhibitor, PP5. Moreover, we demonstrate that the urothelium secretes these proteins in a polarized fashion into the urine via a cAMP-and calcium-regulated pathway. Urinary plasminogen activators of ruminants are therefore urothelium derived rather then kidney derived as in some other species; this heterogeneity may have evolved in response to different physiological or dietary factors. In conjunction with our recent finding that transgenic mouse urothelium can secrete ectopically expressed human growth hormone into the urine, our data establish that normal mammalian urothelium can function not only as a permeability barrier but also as a secretor of urinary proteins that can play physiological or pathological roles in the urinary tract.

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“…† Similar concentrations of uPA were found in human (100 -1,000 g͞liter) (ref. 38 and data not shown) and mouse urine (Х1,800 g͞liter) (49).…”

Section: Results and Discussion Upa And Tpa As Major Differentiation mentioning

confidence: 99%

Urothelial function reconsidered: A role in urinary protein secretion

Deng

Ding

Lavker

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Urokinase then becomes a natural inhibitor of abnormal initiation and growth of stone. The quantity and activity of urokinase were evidently downregulated in in vivo (8) and in vitro (24) studies. These findings suggest that a higher urinary excretion of urokinase may play a protective role in preventing calcium urolithiasis formation.…”

Section: Discussionmentioning

confidence: 99%

“…The activity and concentration of urokinase was verified to be lower in stone patients compared with normal subjects (7). Urokinase, originally known as a plasminogen activator, degrades the organic matrix of urinary stones to prevent their complete formation and growth (8). Thus, it is important in averting the development of urinary stones.…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of the urokinase gene 3′-UTR T/C polymorphism and susceptibility to urolithiasis

Liu

Ren

et al. 2013

Biomedical Reports

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Abstract. Urokinase is involved in the processes of initiating urinary stones. Several published case-control studies have examined the relationship of urokinase gene 3'-untranslated region (3'-UTR) T/C polymorphism and urolithiasis, but yielded inconsistent findings. In this study, a comprehensive meta-analysis was conducted by pooling relevant studies to obtain reliable conclusions. Studies focusing on the association between urokinase gene 3'-UTR T/C polymorphism and urolithiasis were retrieved through PubMed, Medline, Web of Science and the China National Knowledge Infrastructure platform without any limit on language, until October 2012. Four independent articles were eventually identified as eligible for the final meta-analysis, involving 1,195 subjects. Crude odds ratios (ORs), as well as 95% confidence intervals (CIs), were assessed for the association by either fixed-or random-effects models using RevMan 5.0 software. Significant associations were noted in the 'TC vs. CC' codominant model for total population (OR=2.53; 95% CI, 1.43-4.46; P=0.001), Asian population (OR=2.46; 95% CI, 1.38-4.40; P=0.002), male (OR=2.98; 95% CI, 1.43-6.21; P=0.004), Hardy-Weinberg equilibrium (HWE) (OR=2.46; 95% CI, 1.38-4.40; P=0.002) and recurrence (OR=2.66; 95% CI, 1.51-4.67; P=0.00). Statistically significant associations were also observed in the 'TT+TC vs. CC' dominant model for the Asian, male, HWE and recurrence population (P<0.05). Additionally, a significant difference was detected in the 'T vs. C' allele model for HWE. However, there were no associations in either the 'TT vs. CC' codominant model or 'TT vs. TC+CC' recessive model. In conclusion, the present meta-analysis suggests that urokinase gene T allele may increase the susceptibility of urolithiasis.

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“…At sites of damage, uPA also may be produced by inflammatory cells and activated fibroblasts. The primary physiologic role of renal uPA is unknown; it might play a role in nephrolithiasis prevention (103). In response to chronic damage that is induced by UUO, renal uPA mRNA levels and protease activity increase despite significant increases in PAI-1 (61,71).…”

Section: Plasminmentioning

confidence: 99%