Role of basic fibroblast growth factor (FGF-2) in diabetic nephropathy and mechanisms of its induction by hyperglycemia in human renal fibroblasts

Vasko, Radovan; Koziolek, Michael; Ikehata, Masami; Rastaldi, Maria Pia; Jung, Klaus; Schmid, Holger; Kretzler, Matthias; Müller, Gerhard A.; Strutz, Frank

doi:10.1152/ajprenal.90352.2008

Cited by 23 publications

(18 citation statements)

References 43 publications

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“…Chronic hyperglycemia stimulates the production of ROS and angiotensin, which in turn accelerates the progression of tubulointerstitial fibrosis (41,101). Experimental data indicate an important role for ROS in the nephropathy of diabetes.…”

Section: Diabetic Nephropathymentioning

confidence: 99%

Peroxisomes and Kidney Injury

Vasko

2016

Antioxidants & Redox Signaling

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Significance: Peroxisomes are organelles present in most eukaryotic cells. The organs with the highest density of peroxisomes are the liver and kidneys. Peroxisomes possess more than fifty enzymes and fulfill a multitude of biological tasks. They actively participate in apoptosis, innate immunity, and inflammation. In recent years, a considerable amount of evidence has been collected to support the involvement of peroxisomes in the pathogenesis of kidney injury. Recent Advances: The nature of the two most important peroxisomal tasks, betaoxidation of fatty acids and hydrogen peroxide turnover, functionally relates peroxisomes to mitochondria. Further support for their communication and cooperation is furnished by the evidence that both organelles share the components of their division machinery. Until recently, the majority of studies on the molecular mechanisms of kidney injury focused primarily on mitochondria and neglected peroxisomes. Critical Issues: The aim of this concise review is to introduce the reader to the field of peroxisome biology and to provide an overview of the evidence about the contribution of peroxisomes to the development and progression of kidney injury. The topics of renal ischemia-reperfusion injury, endotoxin-induced kidney injury, diabetic nephropathy, and tubulointerstitial fibrosis, as well as the potential therapeutic implications of peroxisome activation, are addressed in this review. Future Directions: Despite recent progress, further studies are needed to elucidate the molecular mechanisms induced by dysfunctional peroxisomes and the role of the dysregulated mitochondria-peroxisome axis in the pathogenesis of renal injury. Antioxid. Redox Signal. 25, 217-231.

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Section: Diabetic Nephropathymentioning

confidence: 99%

Peroxisomes and Kidney Injury

Vasko

2016

Antioxidants & Redox Signaling

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“…27,30 Therefore, we sought to detect intraglomerular gene expression of FGF2. However, our glomerular analysis using in situ hybridization of FGF2 and immortalized cell lines showed virtually undetectable increased expression in the diabetic kidney.…”

Section: Glypican-5 In Diabetic Nephropathymentioning

confidence: 99%

“…*P < 0.05, **P < 0.01. ajp.amjpathol.org -The American Journal of Pathology tubulointerstitial injury. 30 Both systemic circulating FGF2 and renal tubulointerstitial FGF2 levels are thought to be the source of FGF2 accumulation in glomeruli.…”

Section: Glypican-5 In Diabetic Nephropathymentioning

confidence: 99%

Glypican-5 Increases Susceptibility to Nephrotic Damage in Diabetic Kidney

Okamoto

Honda

Doi

et al. 2015

The American Journal of Pathology

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Type 2 diabetes mellitus is a leading health issue worldwide. Among cases of diabetes mellitus nephropathy (DN), the major complication of type 2 diabetes mellitus, the nephrotic phenotype is often intractable to clinical intervention and demonstrates the rapid decline of renal function to end-stage renal disease. We recently identified the gene for glypican-5 (GPC5), a cell-surface heparan sulfate proteoglycan, as conferring susceptibility for acquired nephrotic syndrome and additionally identified an association through a genomewide association study between a variant in GPC5 and DN of type 2 diabetes mellitus. In vivo and in vitro data showed a progressive increase of GPC5 in type 2 DN along with severity; the excess was derived from glomerular mesangial cells. In this study, diabetic kidney showed that accumulation of fibroblast growth factor (Fgf)2 strikingly induced progressive proteinuria that was avoided in Gpc5 knockdown mice. The efficacy of Gpc5 inhibition was exerted through expression of the Fgf receptors 3 and 4 provoked in the diabetic kidney attributively. Extraglomerular Fgf2 was pathogenic in DN, and the deterrence of Gpc5 effectively inhibited the glomerular accumulation of Fgf2, the subsequent increase of mesangial extracellular matrix, and the podocytes' small GTPase activity. These findings elucidate the pivotal role of GPC5, identified as a susceptible gene in the genome-wide association study, in hyperglycemia-induced glomerulopathy. Among diabetes mellitus nephropathy (DN) cases, intractable dysfunction rapidly propagating to end-stage renal disease often accompanies the nephrotic proteinuria phenotype. Our recent study implicated glypican-5 (GPC5) as a susceptible gene for acquired nephrotic syndrome and demonstrated its functional significance by using podocyte-specific knockout mice; a genome-wide association study of DN satisfying the criterion of nephrotic syndrome also clarified GPC5 as the candidate gene [odds ratio 1.45 (95% CI, 1.18e1.79)].

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“…This leads to a shift in the composition of the proteins that are over-expressed. For example, hyperglycemia is known to upregulate fibroblast growth factor-2, which bears an IRES in its 5′UTR [40,41,43,44]. Similarly, high glucose leads to translation of CD36, a scavenger receptor that mediates uptake of oxidized low-density lipoprotein, via ribosome re-initiation [42,45].…”

Section: Effects Of Translation On Kidney Function and Diseasesmentioning

confidence: 99%

Mechanisms and Control of Protein Translation in the Kidney

Schaeffer¹,

Abrass²

2009

Am J Nephrol

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Translational control of protein synthesis is critical for cell division, homeostasis and survival. Recent data indicate that dysregulation of protein synthesis that leads to either increased or decreased expression of specific proteins contributes to the manifestations of various kidney diseases. Most of the control of protein synthesis occurs in the first or initiation phase, which is also the most complicated. Following the initiation phase is the elongation phase where the peptide chain is formed. RNA transcripts are released from ribosomes after the termination phase. Transcripts can be translated in a cap-dependent or cap-independent manner. The mTOR (mammalian target of rapamycin) cascade regulates translation of most cap-dependent transcripts at the level of initiation and elongation, which represents 95% of total transcripts. During specific events (e.g. mitosis, stress cell survival) control of the less-common cap-independent transcripts occurs which allows the cell to adapt to the new state. Activation of stress kinases and inactivation of the mTOR pathway are at the center of this adaptive mechanism. Recent studies have elucidated the role of micro-RNAs (miRs) in controlling translation. miRs bind directly to specific transcripts and most often directly reduce translation; however, by targeting other positive or negative regulators of the pathways regulating protein synthesis they may indirectly affect synthetic levels of other transcripts. Several examples are described below in which these mechanisms are intertwined and act together to dysregulate protein synthesis in the diseased kidney.

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Role of basic fibroblast growth factor (FGF-2) in diabetic nephropathy and mechanisms of its induction by hyperglycemia in human renal fibroblasts

Abstract: Vasko R, Koziolek M, Ikehata M, Rastaldi MP, Jung K, Schmid H, Kretzler M, Mü ller GA, Strutz F. Role of basic fibroblast growth factor (FGF-2) in diabetic nephropathy and mechanisms of its induction by hyperglycemia in human renal fibroblasts.

Cited by 23 publications

References 43 publications

Peroxisomes and Kidney Injury

Peroxisomes and Kidney Injury

Glypican-5 Increases Susceptibility to Nephrotic Damage in Diabetic Kidney

Mechanisms and Control of Protein Translation in the Kidney

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