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Megalin-Mediated Specific Uptake of Chitosan/siRNA Nanoparticles in ...
Here we show by real time in vivo fluorescence bioimaging and immunohistological analysis that chitosan/siRNA nanoparticles reside in the kidney for at least 48 hrs, specifically in the proximal tubule epithelial cells (PTECs).
The endocytosis receptor megalin: From bench to bedside
Proximal tubular epithelial cells (PTECs) of the kidney are specialized for the apical endocytosis of glomerular-filtered or PTEC-secreted proteins, peptides, and essential substances to prevent their inefficient loss in the urine. Megalin/low-density lipoprotein (LDL) receptor-related protein 2 is a large (∼600 kDa) glycoprotein member of the LDL receptor family (Saito et al., 1994 ...
The Endocytic Receptor Megalin and its Associated Proteins in Proximal ...
Evidence suggests that megalin and the cubilin-amnionless complex are involved in the uptake of toxic substances into PTECs, which leads to the development of kidney disease. Studies of megalin and its associated molecules will be useful for future development of novel strategies for the diagnosis and treatment of kidney diseases.
Megalin-mediated siRNA uptake in kidney proximal tubule cells
Additionally, we observed colocalization of siRNA molecules and megalin in mouse kidneys from in vivo studies. Elucidating the mechanism (s) for siRNA uptake in the proximal tubule aids in the development of RNAi renal therapeutics and, more broadly, the understanding of class effects associated with siRNA nephrotoxicity.
Targeted Delivery of siRNA to Proximal Tubule Cells in Kidney
In the present study, we investigated siRNA uptake in vitro and in vivo using conjugated siRNAs called STRIKERs . A well-differentiated, opossum kidney (OK) PTEC cell line was used as a model system to mimic proximal tubule biology both morphologically and functionally, for studying siRNA uptake.
Megalin, cubilin, and Dab2 drive endocytic flux in kidney proximal ...
ABSTRACT The kidney proximal tubule (PT) elaborates a uniquely high-capacity apical endo-cytic pathway to retrieve albumin and other proteins that escape the glomerular filtration barrier. Megalin and cubilin/amnionless (CUBAM) receptors engage Dab2 in these cells to mediate clathrin-dependent uptake of filtered ligands.
Megalin and cubilin in proximal tubule protein ... - Kidney International
Proximal tubule protein uptake is mediated by 2 receptors, megalin and cubilin. These receptors rescue a variety of filtered ligands, including biomarkers, essential vitamins, and hormones. Receptor gene knockout animal models have identified important functions of the receptors and have established their essential role in modulating urinary protein excretion. Rare genetic syndromes associated ...
Megalin-mediated siRNA uptake in kidney proximal tubule cells
Additionally, we observed colocalization of siRNA molecules and megalin in mouse kidneys from in vivo studies. Elucidating the mechanism (s) for siRNA uptake in the proximal tubule aids in the development of RNAi renal therapeutics and, more broadly, the understanding of class effects associated with siRNA nephrotoxicity.
Megalin, a multi-ligand endocytic receptor, and its participation in ...
In a high-fat diet-induced animal model of metabolic syndrome, megalin mediates the proximal tubular uptake of nephrotoxic substances such as lipid-modified proteins, causing tubule-glomerular alterations [8]. Megalin also facilitates the reabsorption of nephrotoxic drugs like aminoglycosides, polymyxin B, and colistin [7].
Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in ...
Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing.
Megalin-Mediated Specific Uptake of Chitosan/siRNA Nanoparticles in ...
le in kidney specific accumulation of siRNA. In the current study we also investigated the mechanism for chitosan/siRNA deli ery into PTECs. In principle, antisense oligonucleotides can be taken up both at the capillary and tubular lumen sides of the kidney [39;40]. Uptake of solutes from the tubular lumen side of PTECs is often mediated by the ...
School of Pharmacy Startup Develops Promising Kidney-Targeting Drug ...
RENTAC targets the kidney via the megalin receptor family – an endogenous cell-surface receptor family expressed at high levels on the apical side of proximal tubule epithelial cells (PTECs), resulting in the internalization of the conjugated molecules.