Urinary excretion of IGFBP-1 and -3 correlates with disease activity and differentiates focal segmental glomerulosclerosis and minimal change disease

Worthmann, Kirstin; Peters, Imke; Kümpers, Philipp; Saleem, Moin A.; Becker, Jan U.; Agustian, Putri A.; Achenbach, Johannes; Haller, Hermann; Schiffer, Mario

doi:10.3109/08977190903512594

Cited by 20 publications

(12 citation statements)

References 25 publications

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“…This was achieved by studying ex vivo glomeruli of 6 week‐old wild‐type mice given an IGF‐II analogue [Des(1‐6)IGF‐II; Novozymes] that is unable to bind to, and therefore is not modulated by, the IGFBPs . This is important, as IGFBPs are present locally in the glomerulus , which could prevent native IGF‐II from binding to the IGF‐IR. We then went back to our human podocytes and found that IGF‐II also activated both the PI3K and MAPK pathways in these cells, with kinetics similar to insulin (Figure D, E).…”

Section: Resultsmentioning

confidence: 99%

Insulin‐like growth factor‐II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse

Hale

Welsh²,

Perks³

et al. 2013

The Journal of Pathology

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Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro-survival mechanisms are critically important. Insulin-like growth factor-II (IGF-II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF-II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF-II; it signals to this cell via the IGF-I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF-II transgenic mouse that produces approximately 60% of IGF-II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF-II in the mature podocyte for glomerular health across mammalian species.

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Section: Resultsmentioning

confidence: 99%

Insulin‐like growth factor‐II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse

Hale

Welsh²,

Perks³

et al. 2013

The Journal of Pathology

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“…Until now, the relationship between minimal change disease and primary FSGS is still controversial; whether minimal change disease and primary FSGS represent different diseases or a continuum of one disease with different phenotypes is still unknown. There have been many studies focused on differentiation of the two glomerular diseases, and some investigators claimed several biomarkers that might facilitate the differentiation, [13][14][15][16][17][18][19] including proteins expressed on podocytes and molecules excreted into urine, but none of these biomarkers were confirmed reliable. In this study, we found that the plasma suPAR levels, in part, of our patients with primary FSGS were higher than that in patients with minimal change disease and membranous nephropathy, which indicated that the elevation of plasma suPAR might be related to the pathogenesis of primary FSGS.…”

Section: Discussionmentioning

confidence: 99%

Plasma soluble urokinase receptor levels are increased but do not distinguish primary from secondary focal segmental glomerulosclerosis

Huang

Liu

Zhang

et al. 2013

Kidney International

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In this study, we measured soluble urokinase receptor levels, a possible permeability factor, in the plasma of patients with primary focal segmental glomerulosclerosis (FSGS) and determined their association with clinical and pathological data in 74 patients with primary FSGS. Healthy donors and patients with minimal change disease, membranous nephropathy, and secondary FSGS were used as controls. The plasma-soluble urokinase receptor levels, measured by commercial ELISA kits, of patients with primary FSGS (median: 2923, interquartile range 2205-4360 pg/ml) were significantly higher than those of patients with minimal change disease (median 2050 pg/ml), membranous nephropathy (median 2029 pg/ml), and normal individuals (median 1739 pg/ml). There was no significant difference in plasma-soluble urokinase receptor levels between the 74 patients with primary and 14 patients with secondary FSGS. The soluble urokinase receptor levels increased in the order of tip variant, to a not otherwise specified variant and a cellular variant. The soluble urokinase receptor levels were significantly but negatively correlated with creatinine clearance at presentation but positively correlated with crescent formation in patients with primary FSGS. During follow-up, receptor levels decreased significantly in patients with complete remission. Thus, plasma-soluble urokinase receptor levels did not differentiate primary and secondary FSGS, and although significantly elevated in FSGS, they showed considerable overlap with other glomerular diseases.

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“…IGF-1 treatment accelerates recovery in animal models of AKI, but clinical trials had controversial results [ 78 ]. IGFBP-3 and IGFBP-1 levels are increased in patients with FSGS, but not in patients with MCD [ 89 ]. IGFBP-1 levels are also elevated in the kidneys in a mouse model of experimental IgA glomerulonephritis and in serum of patients with IgA glomerulonephritis.…”

Section: Insulin-like Growth Factors (Igf) and Insulin-like Growthmentioning

confidence: 99%

Role of Receptor Tyrosine Kinase Signaling in Renal Fibrosis

Liu

Zhuang

2016

IJMS

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Renal fibrosis can be induced in different renal diseases, but ultimately progresses to end stage renal disease. Although the pathophysiologic process of renal fibrosis have not been fully elucidated, it is characterized by glomerulosclerosis and/or tubular interstitial fibrosis, and is believed to be caused by the proliferation of renal inherent cells, including glomerular epithelial cells, mesangial cells, and endothelial cells, along with defective kidney repair, renal interstitial fibroblasts activation, and extracellular matrix deposition. Receptor tyrosine kinases (RTKs) regulate a variety of cell physiological processes, including metabolism, growth, differentiation, and survival. Many studies from in vitro and animal models have provided evidence that RTKs play important roles in the pathogenic process of renal fibrosis. It is also showed that tyrosine kinases inhibitors (TKIs) have anti-fibrotic effects in basic research and clinical trials. In this review, we summarize the evidence for involvement of specific RTKs in renal fibrosis process and the employment of TKIs as a therapeutic approach for renal fibrosis.

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Urinary excretion of IGFBP-1 and -3 correlates with disease activity and differentiates focal segmental glomerulosclerosis and minimal change disease

Cited by 20 publications

References 25 publications

Insulin‐like growth factor‐II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse

Insulin‐like growth factor‐II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse

Plasma soluble urokinase receptor levels are increased but do not distinguish primary from secondary focal segmental glomerulosclerosis

Role of Receptor Tyrosine Kinase Signaling in Renal Fibrosis

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