Urinary transforming growth factor-β1 in various types of nephropathy

Muro, Pierina De; Faedda, Rossana; Fresu, Pietro; Masala, A.; Cigni, Alessandro; Concas, Gordiano; Mela, Maria; Satta, Andrea; Carcassi, A; Sanna, Giovanni Maria; Cherchi, Gian Mario

doi:10.1016/j.phrs.2003.10.003

Cited by 52 publications

(53 citation statements)

References 31 publications

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“…Furthermore, there is mounting evidence that urinary protein may directly affect PTC function thus contributing to the pathogenesis of renal fibrosis (35)(36)(37)(38)(39)(40). An increase in urinary TGF-␤1 is associated with proteinuria, and urinary TGF-␤1 levels have been proposed to represent a noninvasive tool to evaluate disease activity (41). More recent studies suggest that reduction in urinary TGF-␤1 may in itself be of therapeutic benefit, contributing to the reno-protective effects of blockade of the reninangiotensin system in diabetic nephropathy (41) and accounting for the added benefit of combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (42,43).…”

Section: Discussionmentioning

confidence: 99%

“…An increase in urinary TGF-␤1 is associated with proteinuria, and urinary TGF-␤1 levels have been proposed to represent a noninvasive tool to evaluate disease activity (41). More recent studies suggest that reduction in urinary TGF-␤1 may in itself be of therapeutic benefit, contributing to the reno-protective effects of blockade of the reninangiotensin system in diabetic nephropathy (41) and accounting for the added benefit of combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (42,43). This suggests that in addition to the direct effects of apical presentation of albumin, which may activate PTC, increases in urinary TGF-␤1 associated with proteinuria may also have direct effects leading to activation of profibrotic effects of TGF-␤1.…”

Section: Discussionmentioning

confidence: 99%

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Polarity of Response to Transforming Growth Factor-β1 in Proximal Tubular Epithelial Cells Is Regulated by β-Catenin

Zhang

Lee

Luo

et al. 2007

Journal of Biological Chemistry

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Transforming growth factor-␤1 (TGF-␤1)-mediated loss of proximal tubular epithelial cell-cell interaction is regulated in a polarized fashion. The aim of this study was to further explore the polarity of the TGF-␤1 response and to determine the significance of R-Smad-␤-catenin association previously demonstrated to accompany adherens junction disassembly. Smad3 signaling response to TGF-␤1 was assessed by activity of the Smad3-responsive reporter gene construct (SBE) 4 -Lux and by immunoblotting for phospho-Smad proteins. Similar results were obtained with both methods. Apical application of TGF-␤1 led to increased Smad3 signaling compared with basolateral stimulation. Association of Smad proteins with ␤-catenin was greater following basolateral TGF␤-1 stimulation, as was the expression of cytoplasmic Triton-soluble ␤-catenin. Inhibition of ␤-catenin expression by small interfering RNA augmented Smad3 signaling. Lithium chloride, a GSK-3 inhibitor, increased expression of ␤-catenin and attenuated TGF-␤1-dependent Smad3 signaling. Lithium chloride did not influence degradation of Smad3 but resulted in decreased nuclear translocation. Smad2 activation as assessed by Western blot analysis and activity of the Smad2-responsive reporter constructs ARE/MF1 was also greater following apical as compared with basolateral TGF␤-1 stimulation, suggesting that this is a generally applicable mechanism for the regulation of TGF-␤1-dependent R-Smads. Caco-2 cells are a colonic carcinoma cell line, with known resistance to the anti-proliferative effects of TGF-␤1 and increased expression of ␤-catenin. We used this cell line to address the general applicability of our observations. Inhibition of ␤-catenin in this cell line by small interfering RNA resulted in increased TGF-␤1-dependent Smad3 phosphorylation and restoration of TGF-␤1 anti-proliferative effects.It is accepted that the rate of progression of renal disease is closely correlated with the degree of interstitial fibrosis. Much of our work has focused on the possible mechanisms of the pathogenesis of interstitial fibrosis and in particular the role of PTC.3 Recent studies have highlighted the role of PTC epithelial-mesenchymal transformation in the genesis of renal interstitial fibrosis (1, 2). Transforming growth factor-␤ (TGF-␤) is an important mediator of the pathogenesis of numerous fibrotic diseases and is known to be an important stimulus driving epithelial-mesenchymal transformation (3). One important step in this process is the loss of cell-cell contact (4). Epithelial cells have discrete specialized regions of cell-cell adhesion comprising the tight junction, which forms the main barrier to paracellular traffic and adherens junctions. We have previously demonstrated that alterations in PTC morphology upon TGF-␤1 stimulation are associated with disassembly of tight and adherens junction complexes (5, 6). Evidence now suggests that the adherens junction is an important target for the regulation of intracellular signaling pathways (reviewed in Ref. Our studies sugge...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Polarity of Response to Transforming Growth Factor-β1 in Proximal Tubular Epithelial Cells Is Regulated by β-Catenin

Zhang

Lee

Luo

et al. 2007

Journal of Biological Chemistry

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“…Increased urinary TGF-β 1 excretion has been reported in patients with IgA nephropathy [16, 17,29,30,31,32,33]. A significant correlation of these levels with the degree of mesangial proliferation, matrix expansion and crescent formation, has also been described [16, 30, 32].…”

Section: Urinary Tgf-β1 Levels In Patients With Various Types Of Renamentioning

confidence: 99%

Accurate Measurement and Clinical Significance of Urinary Transforming Growth Factor-Beta<sub>1</sub>

Tsakas

Goumenos

2006

Am J Nephrol

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Transforming growth factorβ₁ (TGF-β₁) is the main modulator of the healing process after tissue injury. In the kidney, if TGF-β₁ release is not switched off, extracellular matrix components (ECM) are accumulated and tissue fibrosis occurs. Urinary TGF-β₁ levels reflect its renal production and it has been determined in various types of glomerular disease. In this review, a critical analysis of the different immunoassays that have been used for the measurement of TGF-β₁ in the urine is presented and the importance of the serial determination of urinary TGF-β₁ levels in patients with various types of renal disease is discussed.

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“…Thus, the urinary TGF-β1 level probably reflects renal TGF-β1 expression. Previous studies have noted the increased level of urinary TGF-β1 in patients with IgA nephritis, focal glomerulonephritis [10,11], and diabetic nephropathy [9], and the urinary TGF-β1 levels were found to be significantly correlated with the grade of interstitial fibrosis in glomerular diseases and the grade of the mesangial matrix increase in proliferative-type diseases [10]. Based on these reports, the increase in the urinary TGF-β1 levels of CRF cats indicates that such changes exist in the kidneys.…”

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confidence: 98%

“…In the present study, cats were selected based on abnormalities seen by blood chemical examination, so it was not known at which stage elevation of urinary TGF-β1 begins. Since the urinary TGF-β1 level reflects the degree of renal lesions [10,11], it may increase in advance of clinical signs or the elevation of BUN and creatinine levels. Further investigation using a large number of cats, especially aged ones, is necessary to determine whether urinary TGF-β1 can be used as an early diagnostic marker of feline CRF.…”

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confidence: 99%

Urinary Transforming Growth Factor-.BETA.1 in Feline Chronic Renal Failure

Arata

Ohmi

Mizukoshi

et al. 2005

The Journal of Veterinary Medical Science

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ABSTRACT. Transforming growth factor-β1 (TGF-β1), an inflammatory cytokine, plays a role in tissue fibrosis, such as glomerular sclerosis and tubulointerstitial fibrosis of the kidneys. In the present study, the urinary TGF-β1 level of cats diagnosed with chronic renal failure (CRF) was measured to investigate its relationship to the pathogenesis of feline CRF. Urinary TGF-β1 levels (TGF-β1/creatinine ratio) were significantly increased compared with healthy controls, whereas serum levels of TGF-β1 were not. These results indicate that TGF-β1 is expressed in the kidneys of CRF cats, and that it was reflected in the urinary TGF-β1 level. Therefore, TGF-β1 may play a role in feline CRF, and urinary TGF-β1 could be used as a clinical marker for renal fibrosis. KEY WORDS: CRF, fibrosis, TGF-β1.

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Urinary transforming growth factor-β1 in various types of nephropathy

Cited by 52 publications

References 31 publications

Polarity of Response to Transforming Growth Factor-β1 in Proximal Tubular Epithelial Cells Is Regulated by β-Catenin

Polarity of Response to Transforming Growth Factor-β1 in Proximal Tubular Epithelial Cells Is Regulated by β-Catenin

Accurate Measurement and Clinical Significance of Urinary Transforming Growth Factor-Beta<sub>1</sub>

Urinary Transforming Growth Factor-.BETA.1 in Feline Chronic Renal Failure

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