Myofibroblast phenotypes expression in experimental renal scarring

Muchaneta-Kubara, E. C.; Nahas, A. Meguid El

doi:10.1093/ndt/12.5.904

Cited by 101 publications

(81 citation statements)

References 2 publications

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“…PCNA is one of the proteins involved in cell proliferation and DNA synthesis, and an increase in PCNA expression is a marker of glomerular sclerosis and tubulointerstitial injury. In addition, the expression of desmin as a marker of podocyte injury [23][24][25] was significantly increased in the vehicle-treated SHR/NDmcr-cp group than in the WKY/Izm group. Previous studies have shown that podocyte damage is an early event leading to glomerulosclerosis and tubulointerstitial damage in Zucker obese rats with type II diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective effects of an angiotensin II receptor blocker in experimental model rats with hypertension and metabolic disorders

et al. 2009

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Metabolic syndrome (MS) is an independent risk factor for chronic kidney diseases. As the renin-angiotensin system (RAS) is known to have a key role in renal damage, blockade of RAS may show renoprotective effects in MS. In this study, we investigated the renoprotective effects and mechanisms of action of an angiotensin receptor blocker (ARB) in spontaneously hypertensive (SHR/NDmcr-cp) rats as a model of MS. Male SHR/NDmcr-cp rats at 9 weeks of age were divided into three groups, each of which was treated for 12 weeks with vehicle, hydralazine (7.5 mg kg À1 per day, p.o.) or ARB (olmesartan, 5 mg kg À1 per day, p.o.). Blood pressure and urinary protein (UP) excretion were monitored. Kidney tissues were subjected to histological, immunohistochemical and molecular analyses. UP excretion increased with age in vehicle-treated SHR/NDmcr-cp rats compared with that in age-matched WKY/Izm rats. In addition, there was significant glomerular damage (increased glomerular sclerosis index, desmin staining and proliferating cell nuclear antigen (PCNA)-positive cells, electron microscopic findings of podocyte injury) and tubulointerstitial damage (increased tubulointerstitial fibrosis index, type IV collagen staining, PCNA-positive cells and expression of TGF-b mRNA) in vehicle-treated SHR/NDmcr-cp rats compared with that in control rats. All the findings that related to glomerular and tubulointerstitial damage were significantly improved by ARB. Hydralazine mitigated the observed renal damage but was much less effective than ARB, despite similar decreases in blood pressure. There were no significant differences in glucose and lipid metabolism among vehicle-treated, hydralazine-treated and ARB-treated SHR/NDmcr-cp animals. These data suggest that RAS is deeply involved in the pathogenesis of renal damage in MS, and ARBs could provide a powerful renoprotective regimen for patients with MS.

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Section: Discussionmentioning

confidence: 99%

Renoprotective effects of an angiotensin II receptor blocker in experimental model rats with hypertension and metabolic disorders

et al. 2009

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“…However, although some studies have suggested that markers of renal cell activation and proliferation such as immunostaining of renal biopsies for a-SM-actin and PCNA might be useful diagnostic and/or prognostic indicators in glomerular diseases (3)(4)(5), other studies have shown that these immunohistochemical changes observed during renal disease may be reversible (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…There is some experimental evidence suggesting that transforming growth factor-ß (TGF-ß) and platelet-derived growth factor (PDGF) can induce phenotypic modifications of these cells (9,10). The a-SM-actin synthesis upregulated by these cells is frequently associated with increased cell proliferation and increased extracellular matrix production (1,5,8,11). PCNA is an acidic nuclear protein whose levels are increased from the late G1 to the S phase of the cell cycle and whose detection parallels other standard methods of assessing cell proliferation such as BrdU labeling and Ki-67 staining (12,13).…”

Section: Introductionmentioning

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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“…It is well known that the cell type responsible for most ECM synthesis is the myofibroblast, distinguished by the acquisition of a α-SMA phenotype. In normal kidney, α-SMA is expressed exclusively in the intrarenal arteries; however, in a number of glomerulonephritis models, mesangial cells are activated into α-SMA positive myofibroblasts and proliferate, producing excessive ECM in glomeruli [3][4][5][6] . In the present study, Western blot analysis showed that α-SMA expression was increased in the renal cortex of nephrectomized rats and that it was decreased with atRA treatment.…”

Section: Wwwchinapharcom Liu X Et Almentioning

confidence: 99%

“…In various types of glomerular injuries, mesangial cells are activated into ECM-producing myofibroblasts that undergo proliferation. These cells are phenotypically defined by their expression of α-smooth muscle actin (α-SMA) [3][4][5][6] . Recently, plasminogen activator inhibitor-1 (PAI-1) has been widely recognized as a key contributor in fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin

et al. 2011

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Aim: To examine the effects of all-trans retinoic acid (atRA) on renal morphology and function as well as on renal plasminogen activator inhibitor-1 (PAI-1) expression and plasmin activity in rats with 5/6 nephrectomy. Methods: Adult male Sprague Dawley rats were given 5/6 nephrectomy or sham operation. Renal function was measured 2 weeks later. The nephrectomized rats were assigned to groups matched for proteinuria and treated with vehicle or atRA (5 or 10 mg/kg by gastric gavage once daily) for the next 12 weeks. Rats with sham operation were treated with vehicle. At the end of the treatments, kidneys were collected for histological examination, Western blot analysis, and enzymatic activity measurements. Results: The 5/6 nephrectomy promoted hypertension, renal dysfunction, and glomerulosclerosis. These changes were significantly reduced in the atRA-treated group. The expressions of PAI-1 and α-smooth muscle actin (α-SMA) were significantly increased in the vehicle-treated nephrectomized rats. Treatment with atRA significantly reduced the expressions of PAI-1 and α-SMA. However, plasmin activity remained unchanged following atRA treatment. Conclusion: Treatment with atRA ameliorates glomerulosclerosis and improves renal function in rats with 5/6 nephrectomy. This is associated with a decrease in PAI-1 and α-SMA, but not with a change in plasmin activity.

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Myofibroblast phenotypes expression in experimental renal scarring

Abstract: Myofibroblasts may play a role in the pathogenesis of glomerulosclerosis, tubulointerstitial fibrosis and vascular sclerosis. Further, the acquisition of new myofibroblastic phenotypes by glomerular and tubular cells may contribute to renal fibrosis.

Cited by 101 publications

References 2 publications

Renoprotective effects of an angiotensin II receptor blocker in experimental model rats with hypertension and metabolic disorders

Renoprotective effects of an angiotensin II receptor blocker in experimental model rats with hypertension and metabolic disorders

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

Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin

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