Cell Biology of the Glomerular Podocyte

Pavenstädt, Hermann; Kriz, Wilhelm; Kretzler, Matthias

doi:10.1152/physrev.00020.2002

Cited by 1,291 publications

(1,319 citation statements)

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“…Herein, we also demonstrated that 1,25(OH)2D3 treatment in nephropathy rats could up-regulate the expressions of nephrin and podocin, α3β1 integrin and α/β-DG, and decrease podocyte loss and FPW, which may lead to improvement in podocytopenia, proteinuria and a decrease in the urinary podocyte number. It has been shown that proteinuria is associated with foot process effacement (25). Moreover, podocyturia is a more sensitive indicator in assessing the degree of glomerular damage than proteinuria in SD rats (26).…”

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 Ameliorates Podocytopenia in Rats with Adriamycin-induced Nephropathy

Min-shu

Zhou

et al. 2010

Intern. Med.

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Objective To investigate the role of α3β1 integrin and α/β-dystroglycan in protective effects of 1,25(OH)2D3 on podocytes in rats with adriamycin-induced nephropathy. Methods Sprague-Dawley rats were randomly divided into three groups: control group (NC), nephropathy group (NE), and nephropathy+1,25(OH)2D3 group (ND). Rats in NE and ND group were injected intravenously with adriamycin (0.1 mg/10 g body weight) to induce nephropathy, and those in ND group were then subcutaneously treated with 1,25(OH)2D3 for 8 weeks. Urinary protein level, number of urine podocytes, foot process width and glomerulosclerotic index were determined. Nephrin and podocin mRNA and protein expressions were determined by RT-PCR and western blot, respectively. Podocyte density and expressions of α3β1 integrin and α/β-dystroglycan (DG) were analyzed by immunohistochemistry and western blot, respectively. Results The increase in proteinuria, podocyturia and width of foot process in NE group were ameliorated after treatment with 1,25(OH)2D3 for 8 weeks. The glomerulosclerotic index was significantly decreased in ND group when compared with NE group. The podocyte density in ND group (10.3 ± 1.64 cells/glomerulus) was significantly higher than that in NE group (8.43 ± 1.75 cells/glomerulus) (p=0.008). 1,25(OH)2D3 treatment could significantly up-regulate the mRNA and protein expressions of nephrin and podocin, and the protein expressions of α3β1 integrin and α/β-DG. Conclusion The expressions of nephrin, podocin, α3β1 integrin and α/β-DG were decreased in rats with nephropathy. However, 1,25(OH)2D3 treatment could significantly up-regulate the expressions of nephrin, podocin, α3β1 integrin and α/β-DG proteins which might suppress podocyte detachment and podocytopenia.

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Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 Ameliorates Podocytopenia in Rats with Adriamycin-induced Nephropathy

Min-shu

Zhou

et al. 2010

Intern. Med.

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“…This filtration takes place in the glomerulus, a specialized knot of blood vessels whose wall forms the filtration barrier and is composed of three layers: the endothelium, glomerular basement membrane, and visceral epithelial cells or podocytes. Podocytes have finger-like projections, called pedicels, or foot processes, that interdigitate with those from neighboring cells and that are separated by a glycoprotein network forming slit pores of~40 nM in width (1). Although the role of these slit pores in filtration is conjectural, there is clear evidence that changes in podocyte morphology are associated with changes in the integrity of the glomerular filter; for example, the loss of podocytes and progressive nephropathy of diabetes (2).…”

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confidence: 99%

“…Although the role of these slit pores in filtration is conjectural, there is clear evidence that changes in podocyte morphology are associated with changes in the integrity of the glomerular filter; for example, the loss of podocytes and progressive nephropathy of diabetes (2). Importantly, congenital forms of nephrotic syndrome are associated with mutations of podocyte-specific genes (1). The limited ability of the podocyte to repair and/or regenerate is believed to be crucial in progressive renal disease (3).…”

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“…Podocytes contain actin and myosin, suggestive of contractile ability; if coupled with mechanosensitivity, these proteins would allow podocytes to react to changes in capillary diameter and thus maintain the patency of Bowman's space in the face of variations in perfusion pressure. Mature podocytes express several types of receptor and second messenger systems (1). Receptors include muscarinic, angiotensin II, prostaglandin E 2 , and atrial natriuretic peptide, which are targeted onto Ca 2ϩ , phospholipase C/inositol 1,4,5-triphosphate (PLC/IP 3 ), cAMP, and cyclic guanosine monophosphate signal cascades.…”

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Human Podocytes Possess a Stretch-Sensitive, Ca2+-Activated K+ Channel

Morton¹,

Hutchinson²,

Mathieson

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Podocytes express many proteins characteristic of smooth muscle, such as actin and myosin. They also express receptors to several vasoactive agents, including acetylcholine and angiotensin II; these phenotypic properties suggest that podocytes are not static entities but may respond to physiologic stimuli. The electrophysiologic properties of a conditionally immortalized human podocyte cell line that expresses the specific podocyte proteins nephrin, podocin, and synaptopodin were examined by patch clamp. Channels that were highly K ϩ -selective and had a conductance of 224 Ϯ 11.5 pS in symmetrical 150 mM K ϩ solutions were identified. Channel activity was Ca 2ϩ -and voltage-dependent, being increased with an increase in Ca 2ϩ or depolarization, and inhibited by penitrem A. The conductance and voltage-and Ca 2ϩ -dependence suggest that this is the largeconductance calcium-activated K ϩ channel, BK (KC-NMA1)-this was supported by reverse transcription-PCR experiments that showed the presence of the BK encoding mRNA, along with expression of KCNMB subunit types 3 and 4. In sections of human glomeruli, immunocytochemistry revealed that BK co-localizes with the podocyte-specific protein nephrin, indicating that these channels are present in native human podocytes. In whole-cell experiments, penitrem A inhibited outward currents to the same extent as tetra-ethyl ammonium (TEA) but did not affect the membrane potential. Channel activity was also increased by applying suction to the patch pipette or by dilution of the bathing medium, indicating that these channels are stretch sensitive. Thus, these channels do not contribute to the resting membrane potential but are activated by a rise in intracellular Ca 2ϩ , membrane depolarization, cell swelling, or membrane stretch. By implication, these results suggest that podocytes may be able to respond to changes in the glomerular capillary pressure and modulate the GFR.

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“…Podocytes are localized in the outer aspect of the basement membrane, and injury of these cells is known to be associated with proteinuria. 16 Cultured podocytes exposed to mechanical stress enhance angiotensin II type 1 receptor gene expression, which results in podocyte injury. 17 In the present study, the desmin staining score, which shows the degree of damaged podocytes, was significantly reduced by irbesartan.…”

Section: Discussionmentioning

confidence: 99%

Combination therapy with irbesartan and efonidipine for attenuation of proteinuria in Dahl salt-sensitive rats

2010

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Angiotensin receptor blockers (ARBs) or T-and L-type calcium channel blockers (CCBs) are useful for glomerular protection; however, the protective effects of combination therapy remain unclear. In this study, Dahl salt-sensitive rats were fed a high-salt diet and were treated daily with placebo, irbesartan (60 mg kg À1 ), efonidipine (30 mg kg À1 ), irbesartan (60 mg kg À1 )+efonidipine (30 mg kg À1 ), amlodipine (3 mg kg À1 ), or irbesartan (60 mg kg À1 )+amlodipine (3 mg kg À1 ) for 4 weeks. Significant reductions in systolic blood pressure were seen in the irbesartan-, efonidipine-and amlodipine-treated groups compared with the placebo-treated group; a further significant reduction was seen in the irbesartan+efonidipine-treated group compared with the irbesartan-treated group. Compared with the placebo-treated group, proteinuria was significantly lower in the irbesartan-and efonidipine-treated groups, but not in the amlodipine-treated group. Furthermore, a significant attenuation of proteinuria in the irbesartan+efonidipine-treated group compared with the irbesartan-treated group was observed; this effect was not observed in the irbesartan+amlodipine-treated group. The glomerulosclerosis index was significantly attenuated by all active treatments except amlodipine. The glomerulosclerosis index in the irbesartan+efonidipine-treated group, but not in the irbesartan+amlodipine-treated group, was significantly lower than that in the irbesartan-treated group. Significant attenuations of gene expressions of p22 phox , transforming growth factor-b, monocyte chemoattractant protein-1 and collegen I were observed in the irbesartan-and efonidipine-treated groups, but not in the amlodipine-treated group. Values for these parameters were reduced to control levels in the irbesartan+efonidipine-treated group. Combination therapy with ARB and T-and L-type CCB might produce a powerful renal protective effect. INTRODUCTIONKidneys have an important role not only in the homeostasis of water and electrolyte balance but also in the regulation of blood pressure. Angiotensin II is a crucial peptide for regulating blood pressure by slow and rapid pressor responses. The main functions of slow response are augmentation of sodium reabsorption in the proximal tubules and release of aldosterone from the adrenal cortex, whereas the main functions of rapid response are direct contractile response in peripheral resistance arteries and enhancement of peripheral noradrenergic neurotransmission. Therefore, blockade of angiotensin II is a useful antihypertensive strategy. In addition, angiotensin II directly increases mesangial matrix formation by stimulating transforming growth factor (TGF)-b expression. 1 Inhibition of angiotensin II function induces dilation of efferent arterioles, and this mechanism contributes to amelioration of glomerular hypertension, resulting in a decrease in mesangial matrix formation. 2 Therefore, blockade of angiotensin II is also useful for preventing glomerular injury.Calcium channel blockers (CCBs), such as angi...

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Cell Biology of the Glomerular Podocyte

Cited by 1,291 publications

References 457 publications

1,25-Dihydroxyvitamin D3 Ameliorates Podocytopenia in Rats with Adriamycin-induced Nephropathy

1,25-Dihydroxyvitamin D3 Ameliorates Podocytopenia in Rats with Adriamycin-induced Nephropathy

Human Podocytes Possess a Stretch-Sensitive, Ca2+-Activated K+ Channel

Combination therapy with irbesartan and efonidipine for attenuation of proteinuria in Dahl salt-sensitive rats

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