Differential expression of collagen IV isoforms in experimental glomerulosclerosis

Bergijk, Eline C.; Alderwegen, Isolde E. Van; Baelde, Hans J.; Heer, Emile de; Funabïki, Kazuhiko; Miyai, Hironobu; Killen, Paul D.; Kalluri, Raghu; Bruijn, Jan A.

doi:10.1002/(sici)1096-9896(199803)184:3<307::aid-path5>3.3.co;2-n

Cited by 10 publications

(15 citation statements)

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“…Mesangial cells synthesize the a1 chain of collagen IV, the normal collagen chain expressed in the mesangium. On the other hand, collagen a3−a5 (IV) mRNA is expressed at the periphery of the glomerular tuft, which is consistent with the idea that components of the GBM primarily originate from vis− ceral epithelial cells [27]. However, mesangial cells have been seen to undergo phenotypic changes, and can produce interstitial collagens during pathological conditions [25].…”

Section: The Glomerulussupporting

confidence: 80%

The Use of Transgenic Animals in the Study of Diabetic Kidney Disease

Wogensen

Krag²,

Chai³

et al. 2005

Horm Metab Res

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Diabetic nephropathy is one of the most common diseases leading to fibrosis and end-stage renal disease (ESRD) world wide. Under normal conditions, a delicate equilibrium exists between synthesis, composition, and removal of extracellular matrix (ECM). If this is disturbed, ECM accumulation and fibrosis may result. The fragile balance between synthesis and removal of ECM is crucial for the prognosis of glomerular as well as interstitial pathological processes. Some features may favor ECM accumulation and progression to ESRD (dialysis and transplantation), whereas other elements may favor ECM removal and resolution (recovery). Pathogenetic mechanisms and the cellular sources of ECM in the glomerular basement membrane as well as in the tubulointerstitial space are still under investigation. Among several growth factors, transforming growth factor beta1 (TGF-beta1) plays a major role. We consider the use of living animals necessary for our understanding of the complex biological processes that occur during the development of ESRD. The present review will discuss the glomerular as well as interstitial accumulation of ECM and the use of transgenic animals in studying the pathogenetic mechanisms with special emphasis on diabetic kidney disease and TGF-beta1.

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Section: The Glomerulussupporting

confidence: 80%

The Use of Transgenic Animals in the Study of Diabetic Kidney Disease

Wogensen

Krag²,

Chai³

et al. 2005

Horm Metab Res

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“…Interestingly, this discrepancy points towards a direct hormonal effect on the permeability of the glomerular wall, which may involve alteration of the composition of the glomerular extracellular matrix. This might be established through quantitative and/or qualitative analysis of production of glomerular matrix components in such alterations, which indeed have been observed in this model [9,[33][34][35]]. An explanation for this phenomenon may lie in the fact that steroids such as oestrogens and androgens bind to DNA via high-affinity nuclear receptors, and act subsequently as modulators of transcription of genes encoding matrix molecules [36,37].…”

Section: Discussionmentioning

confidence: 97%

Differential effects of sex hormones on autoantibody production and proteinuria in chronic graft-versus-host disease-induced experimental lupus nephritis

Griensven

Bergijk

Baelde

et al. 1997

Clinical and Experimental Immunology

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SUMMARYIn patients with systemic lupus erythematosus, the female-to-male ratio is as high as 10:1. Sex hormones are thought to play a role in this difference in susceptibility. In a previous study, we demonstrated a high susceptibility of female mice to the development of glomerulonephritis after induction of chronic graftversus-host disease (GVHD), compared with male mice. In order to unravel further this gender-related difference (C57Bl/10*DBA/2)F 1 hybrid mice were either castrated or ovariectomized and treated with 17b-ethinyloestradiol or testosterone-decanoate preceding the induction of chronic GVHD. Testosterone-decanoate reduced significantly the development of albuminuria in females. In contrast, proteinuria of 17b-ethinyloestradiol-treated female mice was in the same range as that of sham-operated mice. Autoantibody levels against glomerular basement membrane, renal tubular epithelium, dsDNA and ssDNA, as determined by ELISA, were higher in 17b-ethinyloestradiol-treated female mice than in all other groups. Immunofluorescence studies showed the presence of immunoglobulin and complement deposits in glomeruli of all animals, without significant differences between the experimental groups. Our findings confirm earlier observations, in that testosterone-decanoate is shown to be an inhibitory compound, whereas 17b-ethinyloestradiol has stimulating properties in autoimmunity. Moreover, our results show for the first time differential hormonal effects on autoantibody levels and proteinuria in experimental lupus nephritis.

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“…Concurrent with its effect on UACR, PF-03882845 was more potent than eplerenone in suppressing collagen IV gene and protein expression in kidney cortex. Collagen IV has been associated with glomerulosclerosis in experimental models (Floege et al, 1992; Bergijk et al, 1998; Lee et al, 1998) and humans (Kim et al, 1991; Tamsma et al, 1994; Esposito et al, 1996) with kidney disease. Renal biopsies from patients with diabetic nephropathy indicated a clear increase in α 2 type IV collagen gene and protein in glomeruli compared to controls (Adler et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy

et al. 2013

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The mineralocorticoid receptor (MR) antagonists PF-03882845 and eplerenone were evaluated for renal protection against aldosterone-mediated renal disease in uninephrectomized Sprague-Dawley (SD) rats maintained on a high salt diet and receiving aldosterone by osmotic mini-pump for 27 days. Serum K+ and the urinary albumin to creatinine ratio (UACR) were assessed following 14 and 27 days of treatment. Aldosterone induced renal fibrosis as evidenced by increases in UACR, collagen IV staining in kidney cortex, and expression of pro-fibrotic genes relative to sham-operated controls not receiving aldosterone. While both PF-03882845 and eplerenone elevated serum K+ levels with similar potencies, PF-03882845 was more potent than eplerenone in suppressing the rise in UACR. PF-03882845 prevented the increase in collagen IV staining at 5, 15 and 50 mg/kg BID while eplerenone was effective only at the highest dose tested (450 mg/kg BID). All doses of PF-03882845 suppressed aldosterone-induced increases in collagen IV, transforming growth factor-β 1 (Tgf-β 1), interleukin-6 (Il-6), intermolecular adhesion molecule-1 (Icam-1) and osteopontin gene expression in kidney while eplerenone was only effective at the highest dose. The therapeutic index (TI), calculated as the ratio of the EC50 for increasing serum K+ to the EC50 for UACR lowering, was 83.8 for PF-03882845 and 1.47 for eplerenone. Thus, the TI of PF-03882845 against hyperkalemia was 57-fold superior to that of eplerenone indicating that PF-03882845 may present significantly less risk for hyperkalemia compared to eplerenone.

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Differential expression of collagen IV isoforms in experimental glomerulosclerosis

Cited by 10 publications

References 0 publications

The Use of Transgenic Animals in the Study of Diabetic Kidney Disease

The Use of Transgenic Animals in the Study of Diabetic Kidney Disease

Differential effects of sex hormones on autoantibody production and proteinuria in chronic graft-versus-host disease-induced experimental lupus nephritis

PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy

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