Reevaluation of glomerular charge selective protein-sieving function

Saito, Hiroshi; Takahashi, Shori; Nagata, Michio; Tsuchiya, Takeshi; Mugishima, Hideo; Kou, Yan; Kondo, Yoshiaki; Matsuyama, Tomohiro; Sekine, Takashi; Igarashi, Takashi

doi:10.1007/s00467-008-1013-9

Cited by 7 publications

(3 citation statements)

References 14 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The renal proximal tubule of the kidney is a major site where reabsorption of proteins and other substances (e.g., carrier-bound vitamins and trace elements) from glomerular filtrates are facilitated via endocytosis 19, 20, 21. To develop potential molecular probes with high efficiency for not only diagnosis but also potential targeted drug delivery, we thus aimed to preferentially select cell-internalizing DNA aptamers with high specificity to CK + cells.…”

Section: Resultsmentioning

confidence: 99%

“…In the proximal tubule, reabsorption of proteins and other molecules from the glomerular filtrates is mainly facilitated by receptor-mediated endocytosis, which is mediated by megalin and cubilin membrane receptors under normal conditions. Indeed, efficient reabsorption of proteins and substances from glomerular filtrates is a vital function of RPTECs 19, 21…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Selection of Cell-Internalizing DNA Aptamers in a Model System of Inflammatory Kidney Disease

Ranches

Lukasser

Schramek

et al. 2017

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is a progressive pathological condition marked by a gradual loss of kidney function. Treatment of CKD is most effective when diagnosed at an early stage and patients are still asymptomatic. However, current diagnostic biomarkers (e.g., serum creatinine and urine albumin) are insufficient for prediction of the pathogenesis of the disease. To address this need, we applied a cell-SELEX (systematic evolution of ligands by exponential enrichment) approach and identified a series of DNA aptamers, which exhibit high affinity and selectivity for cytokine-stimulated cells, resembling some aspects of a CKD phenotype. The cell-SELEX approach was driven toward the enrichment of aptamers that internalize via the endosomal pathway by isolating the endosomal fractions in each selection cycle. Indeed, we demonstrated co-localization of selected aptamers with lysosomal-associated membrane protein 1 (LAMP-1), a late endosomal and lysosomal marker protein, by fluorescence in situ hybridization. These findings are consistent with binding and subsequent internalization of the aptamers into cytokine-stimulated cells. Thus, our study sets the stage for applying selected DNA aptamers as theragnostic reagents for the development of targeted therapies to combat CKD.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

In Vitro Selection of Cell-Internalizing DNA Aptamers in a Model System of Inflammatory Kidney Disease

Ranches

Lukasser

Schramek

et al. 2017

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

show abstract

“…The fractional excretion of serum total protein in a patient with congenital nephrotic syndrome of the Finnish type was reported to be only approximately 1% 9 . The fractional excretion of total protein is calculated in the same SCTP.…”

Section: Discussionmentioning

confidence: 96%

Clinical Evaluation Of Protein-Sieving Coefficient In Severe Nephrotic Syndrome

Shimizu

Saito

Takahashi

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: The pathogenesis of nephrotic syndrome is thought to be due to a decrease in protein sieving function in the glomerular capillary wall. However, no research has been conducted on the renal sieving coefficient of serum protein in nephrotic patients. We investigated the renal protein sieving coefficient in pediatric patients with severe nephrotic syndrome.Methods: Thirty pediatric patients (age: 3−20, mean: 9.3, years; 18 male and 12 female) with severe nephrotic syndrome: hypoproteinemia (TP (Total Protein) ≤ 5.0 g/dL), heavy proteinuria (UTP/Cr (Creatinine) >2 g/gCr), and a normal GFR(glomerular filtration rate) (creatinine clearance ≥ 90 mL/min), were studied. The sieving coefficient of the serum total protein (SCTP) was calculated using a simple formula: Total protein clearance/creatinine clearance (%). The correlation with a twenty-four-hour (24hr) urinary protein test corrected by body surface area (24hrUPT/BSA) was analyzed to assess the accuracy of SCTP. For reference, the correlation between 24hrUPT/BSA and UTP/Cr with SCTP was also analyzed, and the differences between these correlation coefficients were statistically examined.Results: The mean ± standard error of SCTP was 0.13 ± 0.017%. The correlation coefficients of SCTP and U-TP/Cr with 24hrUPT/BSA were 0.90 and 0.78, respectively. SCTP had a significantly stronger correlation with 24hrUPT/BSA than U-TP/Cr (p < 0.05).Conclusion: We found that only 0.13% of sieving coefficient dysfunction causes severe nephrotic syndrome. SCTP has a stronger correlation with 24hrUPT/BSA than with UTP/Cr. If nephrotic syndrome is defined as a protein-sieving dysfunction of the glomerular capillary wall, SCTP can be considered a conceptually correct indicator.

show abstract

Coarse-Grained Modeling of Protein Second Osmotic Virial Coefficients: Sterics and Short-Ranged Attractions

et al. 2013

View full text Add to dashboard Cite

A series of coarse-grained models, with different levels of structural resolution, were tested to calculate the steric contributions to protein osmotic second virial coefficients (B(22,S)) for proteins ranging from small single-domain molecules to large multidomain molecules, using the recently developed Mayer sampling method. B(22,S) was compared for different levels of coarse-graining: four-beads-per-amino-acid (4bAA), one-bead-per-amino-acid (1bAA), one-sphere-per-domain (1sD), and one-sphere-per-protein (1sP). Values for the 1bAA and 4bAA models were quantitatively indistinguishable for both spherical and nonspherical proteins, and the agreement with values from all-atom models improved with increasing protein size, making the CG approach attractive for large proteins of biotechnological interest. Interestingly, in the absence of detailed structural information, the hydrodynamic radius (R(h)) along with a simple 1sP approximation provided reasonably accurate values for B(22,S) for both globular and highly asymmetric protein structures, while other 1sP approximations gave poorer agreement; this helps to justify the currently empirical practice of estimating B(22,S) from R(h) for large proteins such as antibodies. The results also indicate that either 1bAA or 4bAA CG models may be good starting points for incorporating short-range attractions. Comparison of gD-crystallin B(22) values including both sterics and short-range attractions shows that 1bAA and 4bAA models give equivalent results when properly scaled to account for differences in the number of surface beads in the two CG descriptions. This provides a basis for future work that will also incorporate long-ranged electrostatic attractions and repulsions.

show abstract

Reevaluation of glomerular charge selective protein-sieving function

Cited by 7 publications

References 14 publications

In Vitro Selection of Cell-Internalizing DNA Aptamers in a Model System of Inflammatory Kidney Disease

In Vitro Selection of Cell-Internalizing DNA Aptamers in a Model System of Inflammatory Kidney Disease

Clinical Evaluation Of Protein-Sieving Coefficient In Severe Nephrotic Syndrome

Coarse-Grained Modeling of Protein Second Osmotic Virial Coefficients: Sterics and Short-Ranged Attractions

Contact Info

Product

Resources

About