Molecular composition and function of the slit diaphragm: nephrin, the molecule responsible for proteinuria

Kawachi, Hiroshi; Shimizu, Fujio

doi:10.1007/s101570070017

Cited by 17 publications

(15 citation statements)

References 75 publications

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“…The next question that arose was whether the effect of anti-IP-10 is a specific one. Because our group has been producing some mAbs that recognize glomerular antigens (25,44), we have several mAbs with binding activity to rat podocyte. However, most of these mAbs have no biologic activity.…”

Section: Discussionmentioning

confidence: 99%

“…To elucidate the effect of the anti-IP-10 mAb treatment on the podocyte, we analyzed the expression of IP-10 and the functional molecules of podocyte such as nephrin, podocin, and podoplanin. Nephrin (26,41) and podocin (27,42) are critical components of slit diaphragm that interacts adjacent foot processes and functions to maintain the barrier function of the glomerular capillary wall (43,44). Podoplanin is believed to be a critical molecule for maintaining the foot process structure of podocyte (45).…”

Section: Discussionmentioning

confidence: 99%

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IFN-Inducible Protein-10 Has a Differential Role in Podocyte during Thy 1.1 Glomerulonephritis

Han¹,

Koike²,

Nakatsue³

et al. 2003

Journal of the American Society of Nephrology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

IFN-Inducible Protein-10 Has a Differential Role in Podocyte during Thy 1.1 Glomerulonephritis

Han¹,

Koike²,

Nakatsue³

et al. 2003

Journal of the American Society of Nephrology

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“…It is coming to be accepted that the glomerular visceral epithelial cell (podocyte) plays a role as a final barrier of glomerular capillary wall for retaining plasma proteins [1][2][3]. The podocytes are highly differentiated cells, which form multiple interdigitating foot processes [4].…”

Section: Introductionmentioning

confidence: 99%

Slit diaphragm dysfunction in proteinuric states: identification of novel therapeutic targets for nephrotic syndrome

et al. 2009

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Several recent studies have demonstrated that the slit diaphragm of the glomerular epithelial cell (podocyte) is the structure likely to be the principal barrier in the glomerular capillary wall. Nephrin identified as a gene product mutated in congenital nephrotic syndrome located at the outer leaflet of plasma membranes of the slit diaphragm. The anti-nephrin antibody is capable of inducing massive proteinuria, which indicates that nephrin is a key functional molecule in the slit diaphragm. Expression of nephrin was reduced in glomeruli of minimal change nephrotic syndrome. Some recent studies demonstrated that podocin, CD2-associated protein and NEPH1 are also functional molecules in the slit diaphragm, and their expressions are altered in membranous nephropathy and also in focal glomerulosclerosis. These observations suggested that the alteration of the molecular arrangement in the slit diaphragm is involved in the development of proteinuria in several kinds of glomerular diseases. Recent studies of our group have demonstrated that type 1 receptor-mediated angiotensin II action reduced the expression of the slit diaphragm-associated molecules and that type 1 receptor blockade ameliorated proteinuria by preventing the function of angiotensin II on the slit diaphragm. By the subtraction hybridization techniques using glomerular cDNA of normal and proteinuric rats, we detected that synaptic vesicle protein 2B and ephrin B1 are involved in the maintenance of the barrier function of the slit diaphragm.

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“…In the past several years, some molecules were reported to be associated with the slit diaphragm (8 -11). Nephrin is considered to be a critical component of the slit diaphragm for maintaining the barrier function (9,(12)(13)(14)(15). CD2AP is reported to be associated with nephrin (16).…”

Section: Kawachi@medniigata-uacjpmentioning

confidence: 99%

Cloning of Rat Homologue of Podocin

Kawachi¹,

Koike²,

Kurihara

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Podocin is identified as a product of the gene mutated in a patient with autosomal recessive steroid-resistant nephrotic syndrome. Although podocin is reported to be located at the slit diaphragm area, the precise role of podocin for maintaining the barrier function of the slit diaphragm has not been clearly elucidated. A rat homologue of podocin was cloned, and the expression of podocin was investigated and then compared with the nephrin and the ZO-1 expressions in rat experimental proteinuric models and in developing glomeruli. Amino acid sequences of rat and human podocin are highly homologous (84.3% identity). The domain structure of podocin is also highly conserved between rat and human. The mRNA expression for podocin was detected in glomeruli and the nerve tissues. The localization of podocin has close proximity to that of nephrin in normal adult rat glomeruli. Podocin staining was restricted to the basal side of the podocyte of the early developing stage, whereas nephrin staining was detected on the basolateral surface of podocyte. The redistribution of podocin was observed in the anti-nephrin antibody (ANA)-induced nephropathy and puromycin aminonucleoside (PAN) nephropathy. The redistribution of podocin paralleled with nephrin in ANA nephropathy but not in PAN nephropathy. Podocin is observed at the site of tight junction newly formed in proteinuric state in PAN nephropathy. It is postulated that podocin is one of the critical components of a slit diaphragm for maintaining the barrier function of the glomerular capillary wall. kawachi@med.niigata-u.ac.jpThe primary barrier for ultrafiltration of plasma in a glomerular capillary wall comprises three layers: a fenestrated endothelial cell, a glomerular basement membrane (GBM), and a glomerular epithelial cell (podocyte). Although the role of the GBM in restricting the presence of macromolecules has been emphasized for nearly two decades (1,2), several recent studies have shown that slit diaphragms located between the foot processes play the critical role of a barrier to retain macromolecules (3-7). In the past several years, some molecules were reported to be associated with the slit diaphragm (8 -11). Nephrin is considered to be a critical component of the slit diaphragm for maintaining the barrier function (9,(12)(13)(14)(15). CD2AP is reported to be associated with nephrin (16). Boute et al. (17) cloned a novel gene, NPHS2, mutated in patients with autosomal recessive steroid-resistant nephrotic syndrome and reported that this gene product, podocin, is located at the slit diaphragm area (18). Podocin is an integral membrane protein of 383 amino acids, with a single membrane domain forming a hairpin-like structure and with both N-and C-terminal domains in the cytosol. Recent reports indicate that podocin interacts with CD2AP and nephrin (19,20); however, the precise role of podocin for maintaining the barrier function of the slit diaphragm is not yet clarified. To address this, more studies using experimental models would be necessary. We cl...

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Molecular composition and function of the slit diaphragm: nephrin, the molecule responsible for proteinuria

Cited by 17 publications

References 75 publications

IFN-Inducible Protein-10 Has a Differential Role in Podocyte during Thy 1.1 Glomerulonephritis

IFN-Inducible Protein-10 Has a Differential Role in Podocyte during Thy 1.1 Glomerulonephritis

Slit diaphragm dysfunction in proteinuric states: identification of novel therapeutic targets for nephrotic syndrome

Cloning of Rat Homologue of Podocin

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