Cloning of rat nephrin: Expression in developing glomeruli and in proteinuric states

Kawachi, Hiroshi; Koike, Hiroko; Kurihara, Hidetake; Yaoita, Eishin; Orikasa, Michiaki; Shia, Michael A.; Sakai, Tatsuo; Yamamoto, Tadashi; Salant, David J.; Shimizu, Fujio

doi:10.1046/j.1523-1755.2000.00044.x

Cited by 180 publications

(218 citation statements)

References 19 publications

Supporting

Mentioning

199

Contrasting

Unclassified

Order By: Relevance

“…The situation dramatically changed after saponin pretreatment, which caused a disruption of the slit diaphragm and overall foot process architecture ( Figure 3D). Consistent with a recent study, 29 nephrin was still present at the slit diaphragm of TX-100-extracted rat glomeruli as revealed by Figure 3. Transmission electron microscopy of isolated rat glomeruli.…”

Section: The Slit Diaphragm Itself Is Detergent-resistant In a Cholessupporting

confidence: 92%

“…The extracted tissue was then processed for transmission electron microscopy. As has been shown previously, 1,26,29,30 the slit diaphragms exhibited a remarkable resistance against TX-100 treatment. Although most podocyte foot processes detached from the glomerular basement membrane and most areas on the podocyte plasma membrane were extracted, the slit diaphragms remained mostly intact ( Figure 3B).…”

Section: The Slit Diaphragm Itself Is Detergent-resistant In a Cholessupporting

confidence: 78%

“…8,29 The hallmark of these events is the downward migration of apical tight junctions along with their conversion into slit diaphragms. 1,26 A retrograde conversion is observed in pathological situations in humans extensively studied with the use of rat experimental models.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of Lipid Rafts in Nephrin Phosphorylation and Organization of the Glomerular Slit Diaphragm

Simons

Schwarz

Kriz

et al. 2001

The American Journal of Pathology

146

126

View full text Add to dashboard Cite

NPHS1 has recently been identified as the gene whose mutations cause congenital nephrotic syndrome of the Finnish type. The respective gene product nephrin is a transmembrane protein expressed in glomerular podocytes and primarily localized to the glomerular slit diaphragm. This interpodocyte junction functions in the glomerular filtration by restricting the passage of plasma proteins into the urinary space in a size-selective manner. The functional role of nephrin in this filtration process is so far not very well understood. In this study, we show that nephrin associates in an oligomerized form with signaling microdomains, also known as lipid rafts, and that these localize to the slit diaphragm. We also show that the nephrin-containing rafts can be immunoisolated with the 27A antibody recognizing a podocyte-specific 9-Oacetylated GD3 ganglioside. In a previous study it has been shown that the in vivo injection of this antibody leads to morphological changes of the filtration slits resembling foot process effacement. Here, we report that, in this model of foot process effacement, nephrin dislocates to the apical pole of the narrowed filtration slits and also that it is tyrosine phosphorylated. We suggest that lipid rafts are important in the spatial organization of the glomerular slit diaphragm under physiological and pathological conditions. One of the main functions of the kidney is formation of the primary urine in the glomerulus by plasma ultrafiltration. The structural correlate of ultrafiltration is the glomerular capillary wall with its distinctly layered filtration barrier. It consists of the fenestrated vascular endothelium, the glomerular basement membrane, and a layer of morphologically highly specialized epithelial cells, podocytes.Podocytes form a tight network of multiple interdigitating cellular extensions, called foot processes, which are bridged by so-called "slit diaphragms." 1 The filtration barrier is freely permeable for water, small solutes, and ions but does not allow passage for proteins larger than albumin and other large molecules. The charge selectivity in this process has been attributed to the glomerular basement membrane whereas the slit diaphragm supposedly plays a major role in the size selectivity. 2,3 The importance of the filtration barrier is reflected by a number of human diseases in which the filtration barrier function is disrupted resulting in the loss of plasma proteins into the urine. Patients with persistent proteinuria ultimately develop a nephrotic syndrome with a variety of symptoms including edema, hypoalbuminemia, and hyperlipidemia. 4

show abstract

Section: The Slit Diaphragm Itself Is Detergent-resistant In a Cholessupporting

confidence: 92%

Section: The Slit Diaphragm Itself Is Detergent-resistant In a Cholessupporting

confidence: 78%

See 1 more Smart Citation

Involvement of Lipid Rafts in Nephrin Phosphorylation and Organization of the Glomerular Slit Diaphragm

Simons

Schwarz

Kriz

et al. 2001

The American Journal of Pathology

146

126

View full text Add to dashboard Cite

show abstract

“…Immunohistochemistry was done as previously described according to a modified method using a specific antibody to mAb 5-1-6 antigen which is identical to rat nephrin [32,33]. This antibody was raised in the rabbit against a synthetic peptide sequence derived from the cytoplasmic region of the nephrin protein [32].…”

Section: Quantitation Of Nephrinmentioning

confidence: 99%

“…This antibody was raised in the rabbit against a synthetic peptide sequence derived from the cytoplasmic region of the nephrin protein [32]. These experiments were done using 16 micron frozen kidney sections, as previously reported [34].…”

Section: Quantitation Of Nephrinmentioning

confidence: 99%

Renoprotective effects of vasopeptidase inhibition in an experimental model of diabetic nephropathy

et al. 2003

View full text Add to dashboard Cite

Aims. Although ACE inhibitors slow progression of diabetic renal disease, the mortality and morbidity is still high. As other hormonal factors are involved, inhibition of vasopeptidases could further reduce progression. We studied dual inhibition of angiotensin converting enzyme and neutral endopeptidase in a model of progressive diabetic renal injury. The major endpoints were reductions in systemic blood pressure, albuminuria and renal structural injury. Methods. Diabetic spontaneously hypertensive rats were treated with the ACE inhibitor perindopril (mg·kg −1 · day −1 ) or the vasopeptidase inhibitor omapatrilat at doses of 10 (oma10) and 40 (oma40) mg·kg −1 ·day −1 for 32 weeks. In vivo ACE and NEP inhibition was quantitated by in vitro autoradiography. Renal structural injury was assessed by measurement of the glomerulosclerotic (GS) index and tubulointerstitial area (TI). The expression of transforming growth factor β, β-inducible geneh3 and nephrin were also quantitated.Results. Despite a similar reduction in blood pressure by perindopril and oma10, greater attenuation of albuminuria was afforded by oma10, with a complete amelioration observed with oma40. Oma40 lead to a 33% reduction in renal NEP binding and this was associated with less albuminuria and prevention of GS, TI area and overexpression of TGFβ and βig-h3. Diabetes-associated reduction in nephrin expression was restored by both drugs. Conclusion/Interpretation. These findings suggest that other vasoactive mechanisms in addition to angiotensin II are important in the prevention of diabetic nephropathy, and that vasopeptidase inhibition might confer an advantage over blockade of the RAS alone in the treatment of diabetic renal disease. [Diabetologia (2003) 46:961-971]

show abstract

Nephrin

Holthöfer¹

2002

Wiley Encyclopedia of Molecular Medicine

View full text Add to dashboard Cite

Cloning of rat nephrin: Expression in developing glomeruli and in proteinuric states

Abstract: Nephrin is localized in slit diaphragm in the matured glomeruli and is identical with mAb 5-1-6 antigen. Nephrin is involved in the development of proteinuria not only in mAb 5-1-6 nephropathy, but also in puromycin aminonucleoside nephropathy.

Cited by 180 publications

References 19 publications

Involvement of Lipid Rafts in Nephrin Phosphorylation and Organization of the Glomerular Slit Diaphragm

Involvement of Lipid Rafts in Nephrin Phosphorylation and Organization of the Glomerular Slit Diaphragm

Renoprotective effects of vasopeptidase inhibition in an experimental model of diabetic nephropathy

Nephrin

Contact Info

Product

Resources

About