The Pathogenesis of Focal Segmental Glomerulosclerosis

Jefferson, J. Ashley; Shankland, Stuart J.

doi:10.1053/j.ackd.2014.05.009

Cited by 90 publications

(89 citation statements)

References 58 publications

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“…Focal segmental glomerular sclerosis (FSGS) is a lesion of the kidney glomerulus that leads to nephrotic syndrome, typically progressing to end stage renal disease [Chen and Liapis, 2015; Jefferson and Shankland, 2014; Rood et al, 2012]. The key targets of this lesion are podocytes, highly specialized epithelial cells that enwrap the glomerular capillaries with highly elaborate foot processes [Jefferson and Shankland, 2014].…”

Section: The Role Of Inf2 In Human Diseasementioning

confidence: 99%

“…The key targets of this lesion are podocytes, highly specialized epithelial cells that enwrap the glomerular capillaries with highly elaborate foot processes [Jefferson and Shankland, 2014]. Specialized cell-cell junctions between these foot processes, called slit diaphragms, serve as part of the kidney's filtration barrier.…”

Section: The Role Of Inf2 In Human Diseasementioning

confidence: 99%

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Inverted formins: A subfamily of atypical formins

2017

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Formins are a family of regulators of actin and microtubule dynamics that are present in almost all eukaryotes. These proteins are involved in many cellular processes, including cytokinesis, stress fiber formation, and cell polarization. Here we review one sub-family of formins, the inverted formins. Inverted formins as a group break several formin stereotypes, having atypical biochemical properties and domain organization, and they have been linked to kidney disease and neuropathy in humans. In this review, we will explore recent research on members of the inverted formin sub-family in mammals, zebrafish, fruit flies, and worms.

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Section: The Role Of Inf2 In Human Diseasementioning

confidence: 99%

Section: The Role Of Inf2 In Human Diseasementioning

confidence: 99%

Inverted formins: A subfamily of atypical formins

2017

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“…There are different causes underlying the development of a FSGS pattern, and primary (idiopathic) FSGS has to be distinguished from secondary FSGS caused by known trigger. Regardless of the disease forms, the podocyte stands in the center of the disease and seems to be an important target in FSGS [5]. The pathomechanisms behind the different forms of FSGS disease appears to be similar, resulting in the same histological picture.…”

Section: Introduction: Overview Of Animal Models For Focal Segmental mentioning

confidence: 99%

Recent advances of animal model of focal segmental glomerulosclerosis

Yang

Dettmar

Kronbichler³

et al. 2018

Clin Exp Nephrol

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In the last decade, great advances have been made in understanding the genetic basis for focal segmental glomerulosclerosis (FSGS). Animal models using specific gene disruption of the slit diaphragm and cytoskeleton of the foot process mirror the etiology of the human disease. Many animal models have been developed to understand the complex pathophysiology of FSGS. Therefore, we need to know the usefulness and exact methodology of creating animal models. Here, we review classic animal models and newly developed genetic animal models. Classic animal models of FSGS involve direct podocyte injury and indirect podocyte injury due to adaptive responses. However, the phenotype depends on the animal background. Renal ablation and direct podocyte toxin (PAN, adriamycin) models are leading animal models for FSGS, which have some limitations depending on mice background. A second group of animal models were developed using combinations of genetic mutation and toxin, such as NEP25, diphtheria toxin, and Thy1.1 models, which specifically injure podocytes. A third group of animal models involves genetic engineering techniques targeting podocyte expression molecules, such as podocin, CD2-associated protein, and TRPC6 channels. More detailed information about podocytopathy and FSGS can be expected in the coming decade. Different animal models should be used to study FSGS depending on the specific aim and sometimes should be used in combination.

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“…Further studies revealed that enhanced AT 1 receptor signaling in podocytes leads to proteinuria and FSGS 23 , and inhibition of AT receptors is effective against proteinuria 24, 25 .…”

Section: Introductionmentioning

confidence: 99%

The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling

Ilatovskaya

Palygin

Levchenko

et al. 2017

Sci Rep

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Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca2+ flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II–dependent stimulation of Ca2+ influx in the podocytes is precluded by blocking either AT1 or AT2 receptors (ATRs). Application of Ang(1–7) had no effect on intracellular calcium. Ang II-induced calcium flux was decreased upon inhibition of TRPC channels with SAR7334, SKF 96365, clemizole hydrochloride and La3+, but not ML204. Using a novel 3D whole-glomerulus imaging ex vivo assay, we revealed the involvement of both ATRs in controlling glomerular permeability; additionally, using specific inhibitors and activators of TRPC6, we showed that these channels are implicated in the regulation of glomerular volume dynamics. Therefore, we provide evidence demonstrating the critical role of Ang II/TRPC6 axis in the control of glomeruli function, which is likely important for the development of glomerular diseases.

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The Pathogenesis of Focal Segmental Glomerulosclerosis

Cited by 90 publications

References 58 publications

Inverted formins: A subfamily of atypical formins

Inverted formins: A subfamily of atypical formins

Recent advances of animal model of focal segmental glomerulosclerosis

The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling

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