Polycations induce calcium signaling in glomerular podocytes

Rüdiger, Frank; Greger, R.; Nitschke, Roland; Henger, Anna; Mündel, Peter; Pavenstädt, Hermann

doi:10.1046/j.1523-1755.1999.00729.x

Cited by 27 publications

(25 citation statements)

References 25 publications

(1 reference statement)

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“…7,38 PS treatment induces changes in intracellular Ca 2ϩ in cultured podocytes. 29 Here we show that PS induces similar changes in intracellular Ca 2ϩ in isolated glomeruli, correlating with foot process effacement. We cannot determine whether these Ca 2ϩ changes occur exclusively in podocytes due to the inability to label live cells with identity markers.…”

Section: Discussionsupporting

confidence: 57%

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Calcium Mediates Glomerular Filtration through Calcineurin and mTORC2/Akt Signaling

Vassiliadis

Bracken

Matthews

et al. 2011

Journal of the American Society of Nephrology

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Alterations to the structure of the glomerular filtration barrier lead to effacement of podocyte foot processes, leakage of albumin, and the development of proteinuria. To better understand the signaling pathways involved in the response of the glomerular filtration barrier to injury, we studied freshly isolated rat glomeruli, which allows for the monitoring and pharmacologic manipulation of early signaling events. Administration of protamine sulfate rapidly damaged the isolated glomeruli, resulting in foot process effacement and albumin leakage. Inhibition of calcium channels and chelation of extracellular calcium reduced protamine sulfateinduced damage, suggesting that calcium signaling plays a critical role in the initial stages of glomerular injury. Calcineurin inhibitors (FK506 and cyclosporine A) and the cathepsin L inhibitor E64 all inhibited protamine sulfate-mediated barrier changes, which suggests that calcium signaling acts, in part, through calcineurin-and cathepsin L-dependent cleavage of synaptopodin, a regulator of actin dynamics. The mTOR inhibitor rapamycin also protected glomeruli, demonstrating that calcium signaling has additional calcineurinindependent components. Furthermore, activation of Akt through mTOR had a direct role on glomerular barrier integrity, and activation of calcium channels mediated this process, likely independent of phosphoinositide 3-kinase. Taken together, these results demonstrate the importance of calcium and related signaling pathways in the structure and function of the glomerular filtration barrier.

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Section: Discussionsupporting

confidence: 57%

“…29 Figure 2A shows a representative glomerulus before the addition of PS. Three areas are highlighted, with enlarged images of these areas shown as rows 1, 2, and 3.…”

Section: Treatment With Ps Increases Intracellular Calcium Concentratmentioning

confidence: 99%

Calcium Mediates Glomerular Filtration through Calcineurin and mTORC2/Akt Signaling

Vassiliadis

Bracken

Matthews

et al. 2011

Journal of the American Society of Nephrology

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“…More than a decade ago, it was reported that polycations-induced Ca 2ϩ influx might be an early event in the pathogenesis of protamine sulfate-mediated retraction of podocyte foot processes (60). More recently, Ca 2ϩ and related signaling pathways were found to play a critical role in the initial stages of podocyte injury (69).…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor of activated T cells mediates RhoA-induced fibronectin upregulation in glomerular podocytes

Zhu

Aoudjit

et al. 2013

American Journal of Physiology-Renal Physiology

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Glomerulosclerosis is featured by accumulation of the extracellular matrixes in the glomerulus. We showed previously that activation of the small GTPase RhoA in podocytes induces heavy proteinuria and glomerulosclerosis in the mouse. In the current study, we investigated the mechanism by which RhoA stimulates the production of one of the extracellular matrixes, fibronectin, by podocytes, specifically testing the role of nuclear factor of activated T cells (NFAT). Expression of constitutively active RhoA in cultured podocytes activated the fibronectin promoter, upregulated fibronectin protein, and activated NFAT. Expression of constitutively active NFAT in podocytes also activated the fibronectin promoter and upregulated fibronectin protein. RhoA-induced NFAT activation and fibronectin upregulation were both dependent on the calcium/calmodulin pathway and Rho kinase. NFAT activation was also observed in vivo in the rat and mouse models of podocyte injury and proteinuria, and NFAT inhibition ameliorated fibronectin upregulation in the latter. RhoA activation induced a rise of intracellular calcium ion concentration ([Ca2+]i), which was at least in part dependent on the transient receptor potential canonical 6 (TRPC6) cation channel. The results indicate that RhoA activates NFAT by inducing a rise of [Ca2+]i in podocytes, which in turn contributes to fibronectin upregulation. This pathway may be responsible for the pathogenesis of certain glomerular diseases such as hypertension-mediated glomerulosclerosis.

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“…Measurement of [Ca 2ϩ ] i was performed in single IHKE-1 cells with an inverted fluorescence microscope as recently described (29). In short, IHKE-1 cells were incubated with the Ca 2ϩ -sensitive dye fura-2/AM (5 mmol/L; Sigma-Aldrich) for 30 min at 37°C and mounted in a bath chamber on the stage of an inverted microscope.…”

Section: Measurement Of the Free Cytosolic Calcium Concentration ([Camentioning

confidence: 99%

Up-Regulation of Early Growth Response Gene-1 Via the CXCR3 Receptor Induces Reactive Oxygen Species and Inhibits Na+/K+-ATPase Activity in an Immortalized Human Proximal Tubule Cell Line

Bek

Reinhardt

Fischer

et al. 2003

The Journal of Immunology

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The CXCR3 chemokine receptor, a member of the CXCR family, has been linked to a pathological role in autoimmune disease, inflammatory disease, allograft rejection, and ischemia. In the kidney, expression of the CXCR3 receptor and its ligands is up-regulated in states of glomerulonephritis and in allograft rejection, but little is known about the expression and functional role the CXCR3 receptor might play. Here, we study the function of the CXCR3 chemokine receptor in an immortalized human proximal tubular cell line (IHKE-1). Stimulation of the CXCR3 receptor by its selective agonist monokine induced by IFN-γ leads via a Ca2+-dependent mechanism to an up-regulation of early growth response gene (EGR)-1. Overexpression of EGR-1 induces down-regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase and stimulates the generation of reactive oxygen species (ROS) via the NADH/NADPH-oxidase system. EGR-1 overexpression or treatment with monokine induced by IFN-γ resulted in a ROS-dependent inhibition of basolateral Na+/K+-ATPase activity, compromising sodium transport in these cells. Thus, activation of the CXCR3 receptor in proximal tubular cells might disturb natriuresis during inflammatory and ischemic kidney disease via EGR-1-mediated imbalance of ROS.

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Polycations induce calcium signaling in glomerular podocytes

Abstract: The data indicate that polycations increase podocyte [Ca2+]i. The increase of [Ca2+]i may be an early event in the pathogenesis of protamine sulfate-mediated retraction of podocyte foot processes.

Cited by 27 publications

References 25 publications

Calcium Mediates Glomerular Filtration through Calcineurin and mTORC2/Akt Signaling

Calcium Mediates Glomerular Filtration through Calcineurin and mTORC2/Akt Signaling

Nuclear factor of activated T cells mediates RhoA-induced fibronectin upregulation in glomerular podocytes

Up-Regulation of Early Growth Response Gene-1 Via the CXCR3 Receptor Induces Reactive Oxygen Species and Inhibits Na+/K+-ATPase Activity in an Immortalized Human Proximal Tubule Cell Line

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