A population of proximal tubules when isolated from the glomerular kidneys of seawater-adapted (SW) and freshwater-adapted (FW) killifish (Fundulus heteroclitus) spontaneously secrete fluid. Regardless of SW or FW adaptation, Na and Cl are the dominant electrolytes in secreted fluid. Mg concentrations in fluid secreted by both tubules are significantly greater than those in the peritubular bath, and Mg concentrations are inversely related to Na concentrations. Proximal tubules from either SW or FW fish exhibit low transepithelial voltage (-1 to -2 mV) and low transepithelial resistances (20-30 omega.cm2) typical of other vertebrate proximal tubules. Transepithelial diffusion potentials for Na, Cl, Mg, and SO4 suggest that the paracellular pathway is Na selective and impermeable to divalent ions. Consideration of transepithelial electrochemical potential differences for Na, Cl, Mg, and SO4 suggests active transport of Mg, SO4, and Cl in proximal tubules isolated from SW- and FW-adapted fish. The similarities in the functional properties of secretory proximal tubules isolated from SW- and FW-adapted killifish are striking and raise questions about the in vivo role of these tubules in the renal adaptations to seawater and freshwater.
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http://dx.doi.org/10.1152/ajprenal.1992.262.1.F108 | DOI Listing |
Front Med (Lausanne)
January 2025
Department of Internal Medicine, Texas Tech University Health Sciences Centre, Lubbock, TX, United States.
While changes in glomerular function and structure may herald diabetic kidney disease (DKD), many studies have underscored the significance of tubule-interstitial changes in the progression of DKD. Indeed, tubule-interstitial fibrosis may be the most important determinant of progression of DKD as in many forms of chronic glomerulopathies. The mechanisms underlying the effects of tubular changes on glomerular function in DKD have intrigued many investigators, and therefore, the signaling mechanisms underlying the cross-talk between tubular cells and glomerular cells have been the focus of investigation in many recent studies.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Endocrine Medicine, Shanghai Sixth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201306, Chin, China.
Background And Objective: Mitochondria are crucial to the function of renal tubular cells, and their dynamic perturbation in many aspects is an important mechanism of diabetic kidney disease (DKD). Single-nucleus RNA sequencing (snRNA-seq) technology is a high-throughput sequencing analysis technique for RNA at the level of a single cell nucleus. Here, our DKD mouse kidney single-cell RNA sequencing conveys a more comprehensive mitochondrial profile, which helps us further understand the therapeutic response of this unique organelle family to drugs.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. Electronic address:
SLC17A3 localized to the apical membrane of the renal proximal tubules has been implicated in the urinary excretion of drugs and endogenous/exogenous metabolites transported into the tubules by OAT1 and OAT3. Because SLC17A3 mediates the facilitated diffusion of organic anions, which requires a sensitive and rapid assay, no system has been established to evaluate its transport activity in mammalian cells. In this study, we demonstrated that the exposure of cells expressing click beetle luciferase (bLuc) and SLC17A3 to D-luciferin produces marked bioluminescence, which enables the evaluation of SLC17A3 function.
View Article and Find Full Text PDFSci Rep
January 2025
U1248 Pharmacology & Transplantation, Inserm, Univ. Limoges, Limoges, France.
Deciphering the sources of variability in drug responses requires to understand the processes modulating drug pharmacokinetics. However, pharmacological research suffers from poor reproducibility across clinical, animal, and experimental models. Predictivity can be improved by using Organs-on-Chips, which are more physiological, human-oriented, micro-engineered devices that include microfluidics.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
January 2025
Division of Nephrology and Hypertension, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
The kidney is highly metabolically active, and injury induces changes in metabolism that can impact repair and fibrosis progression. Changes in expression of metabolism-related genes and proteins provide valuable data, but functional metabolic assays are critical to confirm changes in metabolic activity. Stable isotope metabolomics are the gold standard, but these involve considerable cost and specialized expertise.
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