Role of Glomerular Endothelial Damage in Progressive Renal Disease

Yamanaka, Nobuaki; Shimizu, Akira

doi:10.1159/000025904

Cited by 30 publications

(31 citation statements)

References 30 publications

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“…1,2 Interestingly, under certain circumstances, spontaneous recovery from glomerular disease may occur. 3,4 In experimental reversible-glomerular-injury models capillary repair was observed, characterized by endothelial cell proliferation, enhanced expression of angiogenic factors and morphological changes consistent with angiogenesis.…”

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confidence: 99%

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Rookmaaker

Smits

Tolboom

et al. 2003

The American Journal of Pathology

161

122

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Glomerular endothelial injury plays an important role in the pathogenesis of renal diseases and is centrally involved in renal disease progression. Glomerular endothelial repair may help maintain renal function. We examined whether bone-marrow (BM)-derived cells contribute to glomerular repair. A rat allogenic BM transplant model was used to allow tracing of BM-derived cells using a donor major histocompatibility complex class-I specific mAb. In glomeruli of chimeric rats we identified a small number of donor-BM-derived endothelial and mesangial cells, which increased in a time-dependent manner. Induction of anti-Thy-1.1-glomerulonephritis (transient mesangial and secondary glomerular endothelial injury) caused a significant, more than fourfold increase in the number of BM-derived glomerular endothelial cells at day 7 after anti-Thy-1.1 injection compared to chimeric rats without glomerular injury. The level of BM-derived endothelial cells remained high at day 28. We also observed a more than sevenfold increase in the number of BM-derived mesangial cells at day 28. BM-derived endothelial and mesangial cells were fully integrated in the glomerular structure. Our data show that BM-derived cells participate in glomerular endothelial and mesangial cell turnover and contribute to microvascular repair. These findings provide novel insights into the pathogenesis of renal disease and suggest a potential role for stem cell therapy.

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confidence: 99%

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Rookmaaker

Smits

Tolboom

et al. 2003

The American Journal of Pathology

161

122

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“…Glomerular capillary and endothelial injury plays an important role in the pathogenesis of renal diseases and is viewed as a crucial factor in disease progression (1)(2)(3)(4). Recent studies of experimental glomerulonephritis (GN) have indicated that impairment of the capillary repair process in glomerular damage may be associated with the continuation of mesangial proliferation and the accumulation of mesangial matrix, which results in the development of glomerular sclerosis and renal dysfunction (5)(6)(7).…”

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confidence: 99%

Vascular Endothelial Growth Factor165 Resolves Glomerular Inflammation and Accelerates Glomerular Capillary Repair in Rat Anti–Glomerular Basement Membrane Glomerulonephritis

Shimizu

Masuda²,

Mori³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Vascular endothelial growth factor (VEGF) is essential for maintenance of the glomerular capillary network. The present study investigated the effects of VEGF in rats with progressive crescentic glomerulonephritis (GN). Necrotizing and crescentic GN was induced in rats by injection of anti-rat glomerular basement membrane (GBM) antibody. The alterations of glomerular capillaries and glomerular VEGF expression were assessed. In addition, the effects of continuous VEGF 165 administration (10 g/100 g per d) on glomerular capillaries, glomerular inflammation, and the course of crescentic GN were examined. The appropriate timing of VEGF administration in progressive GN also was evaluated. In anti-GBM GN, necrotizing and crescentic glomerular lesions occurred by day 7, and newly formed necrotizing lesions reoccurred by week 3. Expression of VEGF was markedly reduced in necrotizing and crescentic lesions. Capillary repair was impaired after capillary destruction in necrotizing and crescentic glomeruli, which rapidly progressed to sclerotic glomeruli with chronic renal failure. In contrast, in the rats that received VEGF 165 administration from day 7, the necrotizing and crescentic lesions recovered and renal function significantly improved in week 4. This was evident by proliferating endothelial cells and glomerular capillary repair. In addition, VEGF administration decreased intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 expression in glomeruli (particularly on endothelial cells), reduced glomerular infiltrating CD8-postive and ED-1-positive cells, and inhibited the newly formed necrotizing lesions. VEGF administration was apparently effective against both the inflammatory and necrotizing glomerular lesions. These results suggest that VEGF administration resolves glomerular inflammation and accelerates glomerular recovery in the progressive necrotizing and crescentic GN. The therapeutic application of VEGF may be clinically useful for severe GN accompanied by extensive glomerular inflammation and endothelial injury.

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“…A third possibility is that, as the glomerular endothelium was partially dark in color and showed irregular thickening in the present study, it is likely that the capillary endothelium is directly damaged and degenerated by the Na 2 HPO 4 solution. Glomerular endothelial injuries inevitably affect mesangial and epithelial cells and presumably modify the progression of renal disease by reciprocally interacting with them 17 . These results show that phosphate-induced glomerular lesions occur with repeated administration of Na 2 HPO 4 solution for 3 days.…”

Section: Discussionmentioning

confidence: 99%

Early Events Involving Glomerular Calcification Induced by Dibasic Sodium Phosphate Solution in Rats

et al. 2008

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Abstract:To investigate the early changes involved in glomerular calcification, 360 mM Na 2 HPO 4 was administered to rats at 8 mL/kg once daily via the tail vein singly or repeatedly. Urinalysis was carried out on days 1, 3, 5 and 8 of dosing, and rats were sacrificed on days 2, 4 and 9 for histopathological and electron microscopic examination of the kidneys. Following single dosing, there were no gross or histological findings, but electron microscopy revealed a number of vacuoles scattered within the Bowman's space. On day 4, minimal and focal mineralization was observed within the parietal epithelial cells. On day 9, mineralization was minimal to mild and localized within the parietal epithelial cells and glomerular basement membrane. Hypertrophy and increased mitotic figures were also frequently observed in the parietal epithelial cells. Low-density lamellar structures with effacement of podocytes, an increased number of microvilli and large amounts of debris filling the Bowman's space were the main electron microscopic changes on days 4 and 9. Increased urinary protein excretion correlated well with the glomerular changes. Immunohistochemically, increased expression of desmin and decreased expression of podoplanin were evident in glomeruli on day 9. The numbers of PCNA-positive podocytes and parietal epithelial cells showed a tendency to increase on day 9. These results suggest that the onset of glomerular calcification is preceded by primary podocyte damage. (J Toxicol Pathol 2008; 21: 229-237)

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Role of Glomerular Endothelial Damage in Progressive Renal Disease

Cited by 30 publications

References 30 publications

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Vascular Endothelial Growth Factor165 Resolves Glomerular Inflammation and Accelerates Glomerular Capillary Repair in Rat Anti–Glomerular Basement Membrane Glomerulonephritis

Early Events Involving Glomerular Calcification Induced by Dibasic Sodium Phosphate Solution in Rats

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