Proximal tubular cell synthesis and secretion of endothelin-1 on challenge with albumin and other proteins

Zoja, Carla; Morigi, Marina; Figliuzzi, Marina; Bruzzi, Isabella; Oldroyd, S.; Benigni, Ariela; Ronco, Pierre; Remuzzi, Giuseppe

doi:10.1016/0272-6386(95)90058-6

Cited by 233 publications

(135 citation statements)

References 29 publications

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“…This fact suggests that the renal handling of protein induced activation of the interstitial cells. It has been suggested that proteins filtered by the glomeruli could be toxic for tubule cells (27)(28)(29). Studies with tubule cell cultures have shown that some proteins such as IgG and albumin induce an increase in the production of inflammatory and vasoactive factors (27,28).…”

Section: Discussionmentioning

confidence: 99%

alpha-Smooth muscle actin and proliferating cell nuclear antigen expression in focal segmental glomerulosclerosis: functional and structural parameters of renal disease progression

Geleilete

Costa

Dantas

et al. 2001

Braz J Med Biol Res

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The aim of the present study was to investigate the expression of asmooth muscle actin (a-SM-actin) and proliferating cell nuclear antigen (PCNA) in renal cortex from patients with focal segmental glomerulosclerosis (FSGS) and their correlations with parameters of renal disease progression. We analyzed renal biopsies from 41 patients with idiopathic FSGS and from 14 control individuals. The a-SMactin immunoreaction was evaluated using a score that reflected the changes in the extent and intensity of staining in the glomerular or cortical area. The PCNA reaction was quantified by counting the labeled cells of the glomeruli or renal cortex. The results, reported as median ± percentile (25th; 75th), showed that the a-SM-actin scores in the glomeruli and tubulointerstitium from the renal cortex were 2.0 (2.0; 4.0) and 3.0 (3.0; 4.0), respectively, in patients with FSGS, and 0.5 (0.0; 1.0) and 0.0 (0.0; 0.5) in the controls. The number of PCNApositive cells per glomerulus and graded field of tubulointerstitium from the renal cortex was 0.2 (0.0; 0.4) and 1.1 (0.3; 2.2), respectively, for patients with FSGS, and 0.0 (0.0; 0.5) and 0.0 (0.0; 0.0) for controls. The present data showed an increase of a-SM-actin and PCNA expression in glomeruli and renal cortex from FSGS patients.The extent of immunoreaction for a-SM-actin in the tubulointerstitial area was correlated with the intensity of proteinuria. However, there was no correlation between the kidney expression of these proteins and the reciprocal of plasma creatinine level or renal fibrosis. These findings suggest that the immunohistochemical alterations may be reversible.

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Section: Discussionmentioning

confidence: 99%

alpha-Smooth muscle actin and proliferating cell nuclear antigen expression in focal segmental glomerulosclerosis: functional and structural parameters of renal disease progression

Geleilete

Costa

Dantas

et al. 2001

Braz J Med Biol Res

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“…Albumin, the most abundant protein in the glomerular filtrate, is endocytosed by proximal tubule cells (7) and can cause direct tubule cell injury in animals (8 -11) and cell culture models (12). Several mechanisms remain under investigation in these experimental settings, including activation of Fas-mediated (12) and peroxisome proliferator-activated receptor-␥-dependent (6) apoptosis, and induction of proinflammatory molecules such as monocyte chemoattractant protein-1 (13,14), osteopontin (13), regulated on activation normal T cell expressed and secreted (15), endothelin-1 (16), , NF-B (18), and fractalkine (10). There is, however, a paucity of mechanistic information in human diseases characterized by chronic proteinuria.…”

mentioning

confidence: 99%

Induction of Renal Tubular Cell Apoptosis in Focal Segmental Glomerulosclerosis

Erkan¹,

Garcia²,

Patterson³

et al. 2005

Journal of the American Society of Nephrology

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The hypothesis that apoptosis represents a proximate mechanism by which tubule cells are damaged in FSGS was tested. Thirty kidney biopsy specimens from children with idiopathic early FSGS were studied retrospectively. Unexpected, apoptosis was evident in both proximal and distal tubule cells. There was a significant correlation between the degree of proteinuria and the number of apoptotic cells. Fas protein was detected predominantly in the tubule cells that underwent apoptosis. When compared with patients with other chronic proteinuric states, those with FSGS displayed a proliferation/ apoptosis ratio in favor of proliferation in the glomerulus but dramatically in favor of apoptosis in the tubules. When both proteinuria and apoptosis were included in a stepwise logistic regression procedure, only apoptosis was found to predict independently the development of ESRD. Prolonged incubation of cultured Madin-Darby canine kidney (distal/collecting) cells with albumin also resulted in a dose-and duration-dependent induction of apoptosis and activation of the Fas pathway, lending support to the novel finding of distal tubule cell apoptosis in patients with FSGS. The results indicate that an elevated tubule cell apoptosis rate at the time of initial biopsy represents an independent predictor of progression to ESRD in patients with early FSGS.

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“…In monolayers of proximal tubular cells, the load with plasma proteins (albumin, IgG and transferrin) induced the synthesis of the vasoconstrictor peptide endothelin-1 (ET-1), a mediator of progressive renal injury by virtue of ability to stimulate renal cell proliferation and extracellular matrix production and to attract monocytes (Zoja et al, 1995). Other investigators confirmed and extended the stimulatory effects of a diversity of plasma proteins on the expression of proinflammatory and profibrotic mediators in renal tubular cells (Yard et al, 2001;Tang et al, 2003).…”

Section: Glomerular Proteinuria As Signal For Interstitial Inflammationmentioning

confidence: 98%

“…Burton et al (1999) discovered that the apical exposure of human proximal tubular cells to 1mg/ml albumin or transferrin did not increase MCP-1 or PDGF-AB release, an effect that was observed after exposure to a human serum fraction (40 to 100 KD) in the molecular weight range similar to albumin and transferrin. Studies that reported the effects of protein overload on NF-activation showed responses from 0.5mg/mL in some experiments and usually >2.5 ->5mg/mL (Zoja et al, 1995;Wang et al, 1997). The latter concentration seems too far exceed the concentration reached in the proteinuric ultrafiltrate in-vivo (Gekle, 2005).…”

Section: Glomerular Proteinuria As Signal For Interstitial Inflammationmentioning

confidence: 99%

Sickle Cell Disease and Renal Disease

Emokpae¹,

Uadia²

2012

Diseases of Renal Parenchyma

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Proximal tubular cell synthesis and secretion of endothelin-1 on challenge with albumin and other proteins

Cited by 233 publications

References 29 publications

alpha-Smooth muscle actin and proliferating cell nuclear antigen expression in focal segmental glomerulosclerosis: functional and structural parameters of renal disease progression

alpha-Smooth muscle actin and proliferating cell nuclear antigen expression in focal segmental glomerulosclerosis: functional and structural parameters of renal disease progression

Induction of Renal Tubular Cell Apoptosis in Focal Segmental Glomerulosclerosis

Sickle Cell Disease and Renal Disease

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