The proximal tubule is divided anatomically into 3 distinct segments-S1 to S3-on the basis of differences in cellular ultrastructure, but the functional processes that define and shape these remain elusive. In a new study, Christensen used 3-dimensional nephron reconstruction, electron microscopy, and antibody staining to precisely map protein uptake to the structure of the proximal tubule. They reported striking axial patterns in endocytosis along the segments, which showed substantial plasticity in disease states.
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http://dx.doi.org/10.1016/j.kint.2020.12.031 | DOI Listing |
Br J Pharmacol
January 2025
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona, USA.
Background And Purpose: Kidney disease (KD) is a leading cause of mortality worldwide, affecting 〉10% of the global population. Two of the most common causes of KD are diabetes and acute kidney injury (AKI), both of which induce mitochondrial dysfunction resulting in renal proximal tubular damage/necrosis. Thus, pharmacological induction of mitochondrial biogenesis (MB) may provide a therapeutic strategy to block the onset/progression of KD.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
February 2025
Calcium Signaling Laboratory, Veterans Affairs Medical Center, Research Service, Washington, District of Columbia, USA.
Crystalline nephropathy (CN) is characterized by deposition of microcrystals within the kidney tubular microstructure, specifically in the renal tubular cells. Nephropathic conditions have been observed in kidney stone patients as nephrocalcinosis, resulting from the deposition of calcium phosphate (CaP) microcrystals mainly within the renal tubule. CaP microcrystals trigger nephrotoxicity and cell death leading to acute and chronic kidney disease and in some cases end stage renal disease.
View Article and Find Full Text PDFExtracell Vesicle
December 2024
The Jared Grantham Kidney Institute at the University of Kansas Medical Center, Department of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Autosomal dominant polycystic kidney (ADPKD) disease is the commonest genetic cause of kidney failure (affecting 1:800 individuals) and is due to heterozygous germline mutations in either of two genes, and . Homozygous germline mutations in are responsible for autosomal recessive polycystic kidney (ARPKD) disease a rare (1:20,000) but severe neonatal disease. The products of these three genes, (polycystin-1 (PC1 4302(3)aa)), (polycystin-2 (PC2 968aa)) and (fibrocystin (4074aa)) are all present on extracellular vesicles (EVs) termed, PKD-exosome-like vesicles (PKD-ELVs).
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas. Electronic address:
In vitro models that can faithfully replicate critical aspects of kidney tubule function such as directional drug transport are in high demand in pharmacology and toxicology. Accordingly, development and validation of new models is underway. The objective of this study was to characterize physiologic and transport functions of various sources of human renal proximal tubule epithelial cells (RPTECs).
View Article and Find Full Text PDFBMC Nephrol
January 2025
Department of Nephrology, Japan Community Healthcare Organization Sendai Hospital, 981-3281, Sendai, Miyagi, Japan.
Background: Oliguric acute kidney injury (AKI) is one of the critical conditions which needs emergent treatment due to the lack of the capacity of excreting toxins and fluids, and plasma membrane bleb formation is considered as one of the characteristic morphologic alterations in ischemic AKI in both animal models and human. We present here an autopsy case with clear electron microscopy images capturing a definitive instance of blebbing in ischemic AKI.
Case Presentation: A 66-year-old man was admitted for oliguric AKI with nephrotic syndrome (NS).
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