Determinants of Vascular Permeability in the Kidney Glomerulus

Hamano, Yuki; Grunkemeyer, James A.; Sudhakar, Akulapalli; Zeisberg, Michael; Cosgrove, Dominic; Morello, Roy; Lee, Brendan; Sugimoto, Hikaru; Kalluri, Raghu

doi:10.1074/jbc.m204806200

Cited by 117 publications

(119 citation statements)

References 49 publications

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“…Vegfr-2 has been shown to be upregulated in the early stage of diabetes, but not in long-term diabetes [27]. Deterioration of the slit diaphragm is associated with decreased glomerular filter integrity [33]. The existence and function of this diaphragm is critically dependent on nephrin and decreased production of this protein has been observed in different types of kidney disease [34,35].…”

Section: Discussionmentioning

confidence: 99%

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

et al. 2007

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Aims/hypothesis An increasing amount of evidence indicates that mannose-binding lectin (MBL) plays a role in the development of diabetic nephropathy. The main objective of the study was to analyse whether MBL influences the effects of diabetes on the kidneys. Materials and methods In one group of wild-type mice and in one group of MBL double knockout mice we induced diabetes by the use of streptozotocin as a model of type 1 diabetes. Two groups of non-diabetic mice, wild-type and MBL knockout, were also included. By two-way ANOVA we evaluated if MBL modulated the effects of diabetes by testing the interaction between diabetes and MBL. Results MBL interacted with the effects of diabetes on three outcome measures: kidney weight (p<0.001), urinary albumin excretion (p=0.001) and the expression of collagen IVα1 (Col4a1) mRNA (p=0.002). This means that the effects that diabetes normally has on these parameters were significantly modified by MBL. MBL showed a tendency to interact with the effects of diabetes on glomerular basement membrane thickness and total mesangial volume (p=0.065 and p=0.063, respectively). Glomerular volume and total mesangial volume were significantly smaller in animals lacking MBL than in wild-type animals (p=0.006 and p=0.047, respectively). Conclusions/interpretation These findings, for the first time, show that the degree of kidney alteration as a consequence of diabetes is modified by MBL. These findings support a pivotal role of MBL in the development of diabetic kidney disease.

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Section: Discussionmentioning

confidence: 99%

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

et al. 2007

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“…In the present study, the level of VEGF-A mRNA was higher in the placebo-treated NMRI mice than in the STZ-diabetic mice, whereas no difference between placebo-treated NMRI mice and STZ-mice was seen when measuring VEGFR-2 mRNA. Nephrin is a molecule located to the slit diaphragm in the glomerulus filtration barrier between the foot-processes of the podocytes, involved in the filtration of molecules into Bowmans capsule (Hamano et al 2002, Wartiovaara et al 2004. In different kidney diseases, defects in the slit diaphragm are followed by a decrease in renal nephrin and proteinuria (Kawachi et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Renal effects of a neutralising RAGE-antibody in long-term streptozotocin-diabetic mice

Jensen¹,

Denner²,

Schrijvers³

et al. 2006

Journal of Endocrinology

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Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of diabetic kidney disease. The actions of AGEs are mediated both through a non-receptor mediated pathway and through specific receptors for AGEs (e.g. RAGE). To explore a potentially specific role for RAGE in renal changes in type 1 diabetes, we examined the renal effects of a neutralising murine RAGE-antibody (ab) in streptozotocin (STZ)-diabetic mice, a model of type 1 diabetes. One group of STZdiabetic mice was treated for two months with the RAGE-ab, while another STZ-diabetic group was treated for the same period with an irrelevant immunoglobulin G (IgG). Two groups of non-diabetic NMRI mice were treated with either RAGE-ab or isotype-matched IgG for two months. Placebo-treated STZ-diabetic mice showed an increase in kidney weight, glomerular volume, basement membrane thickness (BMT), urinary albumin excretion (UAE) and creatinine clearance (CrCl), when compared with non-diabetic controls. In RAGE-abtreated STZ-diabetic mice, the increase in kidney weight and UAE was reduced, while the increase in CrCl was abolished. RAGE-ab administration in NMRI mice caused a reduction in liver weight and an increase in BMT. Renal messenger RNA (mRNA) for connective tissue growth factor and collagen IV 1 was increased in placebo-treated diabetic animals. RAGE-ab treatment had no impact on the expression of these factors. The renal effects of RAGE-ab administration in STZ-diabetic mice were seen without impact on body weight, blood glucose or food consumption. In conclusion, the present data support the hypothesis that RAGE is an important pathogenic factor in the renal changes in an animal model of type 1 diabetes.

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“…11. In glomeruli of WT mice, ␣1 and ␣2 chain isoforms of type IV collagen are preferentially localized to the mesangial matrix, and the ␣3 and ␣5 chains reveal specific expression in the GBM (Fig.…”

Section: Ultrastructural Analysis Reveals That Bmt Repairs Gbm and Pomentioning

confidence: 99%

Bone-marrow-derived stem cells repair basement membrane collagen defects and reverse genetic kidney disease

Sugimoto

Mundel

Sund

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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228

174

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Type IV collagen is a predominant component of basement membranes, and glomeruli of a kidney filter Ϸ70 -90 liters of plasma every day through a specialized glomerular basement membrane (GBM). In Alport syndrome, a progressive disease primarily affecting kidneys, mutations in GBM-associated type IV collagen genes (COL4A3, COL4A4, or COL4A5) lead to basement membrane structural defects, proteinuria, renal failure, and an absence of all three GBM collagen triple helical chains because of obligatory posttranslational assembly requirements. Here, we demonstrate that transplantation of wild-type bone marrow (BM) into irradiated COL4A3 ؊/؊ mice results in a possible recruitment of BM-derived progenitor cells as epithelial cells (podocytes) and mesangial cells within the damaged glomerulus, leading to a partial restoration of expression of the type IV collagen ␣3 chain with concomitant emergence of ␣4 and ␣5 chain expression, improved glomerular architecture associated with a significant reduction in proteinuria, and improvement in overall kidney histology compared with untreated COL4A3 ؊/؊ mice or irradiated COL4A3 ؊/؊ mice with BM from adult COL4A3 ؊/؊ mice. The ␣3(IV) collagen produced by BM-derived podocytes integrates into the GBM and associates with other ␣-chains to form type IV collagen triple helical networks. This study demonstrates that BM-derived stem cells can offer a viable strategy for repairing basement membrane defects and conferring therapeutic benefit for patients with Alport syndrome.Alport syndrome ͉ bone marrow transplantation ͉ glomerular basement membrane ͉ type IV collogen ␣3 chain ͉ glomeruli

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Determinants of Vascular Permeability in the Kidney Glomerulus

Cited by 117 publications

References 49 publications

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

Renal effects of a neutralising RAGE-antibody in long-term streptozotocin-diabetic mice

Bone-marrow-derived stem cells repair basement membrane collagen defects and reverse genetic kidney disease

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