scholarly journals Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury

2021 ◽  
Author(s):  
Ryo Kawakami ◽  
Miki Matsui ◽  
Ayumu Konno ◽  
Ryosuke Kaneko ◽  
Shreya Shrestha ◽  
...  
Keyword(s):  
Liver Injury ◽  
Proximal Tubular ◽  
Protein Reabsorption

scholarly journals Long-term protein exposure reduces albumin binding and uptake in proximal tubule-derived opossum kidney cells.

1998 ◽  
Vol 9 (6) ◽  
pp. 960-968 ◽  
Author(s):  
M Gekle ◽  
S Mildenberger ◽  
R Freudinger ◽  
S Silbernagl
Keyword(s):  
Amino Acids ◽  
Proximal Tubule ◽  
Uptake Rate ◽  
Kidney Cells ◽  
Proximal Tubular Cells ◽  
Opossum Kidney ◽  
Tubular Cells ◽  
Opossum Kidney Cells ◽  
Proximal Tubular ◽  
Protein Reabsorption

To avoid renal loss of large amounts of proteins, filtered proteins are reabsorbed by endocytosis along the proximal tubule. However, although protein reabsorption is a task of proximal tubular cells, it is also a threat because it may cause cell injury. This study determines whether exposure to bovine serum albumin (BSA) leads to regulatory changes in endocytosis of FITC-BSA in proximal tubule-derived opossum kidney cells. Preincubation with BSA led to a decrease of FITC-BSA endocytosis with an IC50 value of 0.58 g/L. Specific binding of FITC-BSA to the apical membrane was also reduced (IC50 = 0.69 g/L). Kinetic analyses revealed that maximal uptake rate and maximal binding capacity were decreased with no change in affinity. Similar effects were observed after preincubation with equimolar amounts of other proteins (lactalbumin, transferrin, and conalbumin), but not after preincubation with dextran. The effect of preincubation with BSA could be mimicked by preincubation with some amino acids. Preincubation with L-Ala, L-Gln, or NH4Cl, but not with L-Leu, L-Glu, or L-Asp, reduced FITC-BSA endocytosis and binding. Preincubation with BSA, but not with dextran, reduced protein degradation and increased ammonia production, vesicular pH, as well as the rate of lactate dehydrogenase release. Apical fluid-phase endocytosis and apical uptake of neutral amino acids were not reduced. It is concluded that proximal tubular cells reduce the uptake rate for proteins, but not for other substrates, in response to increased protein load. This reduction is achieved by reducing the number of apical binding sites, partially in response to increased ammoniagenesis with deranged vesicular pH and enzyme activities. Thus, increased protein filtration could result in reduced protein reabsorption, thereby enhancing proteinuria.

Receptor-mediated endocytosis of albumin in cultured opossum kidney cells: a model for proximal tubular protein reabsorption

1991 ◽  
Vol 418 (4) ◽  
pp. 383-392 ◽  
Author(s):  
Johann S. Schwegler ◽  
Bernd Heppelmann ◽  
Sigrid Mildenberger ◽  
Stefan Silbernagl
Keyword(s):  
Kidney Cells ◽  
Opossum Kidney ◽  
Receptor Mediated Endocytosis ◽  
Opossum Kidney Cells ◽  
Proximal Tubular ◽  
Protein Reabsorption

scholarly journals Transfer of hepatocellular microRNA regulates cytochrome P450 2E1 in renal tubular cells

2020 ◽  
Author(s):  
Olivia Matthews ◽  
Emma E Morrison ◽  
John D Tranter ◽  
Philip Starkey Lewis ◽  
Iqbal S Toor ◽  
...  
Keyword(s):  
Liver Injury ◽  
Cardiac Injury ◽  
Proximal Tubular Cell ◽  
Tubular Cell ◽  
New Paradigm ◽  
Knock Out ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Proximal Tubular ◽  
Kidney Tubular Cells

AbstractExtracellular microRNAs have been demonstrated to have the ability to enter kidney tubular cells and modify gene expression. We have used a Dicer-hepatocyte-specific microRNA conditional knock-out (Dicer-CKO) mouse to investigate functional microRNA transfer from liver to kidney under physiological conditions and in the context of drug toxicity. Dicer-CKO mice demonstrated a time-dependent decrease in the hepatocyte-derived microRNA, miR-122, in the kidney in the absence of other microRNA changes. During hepatotoxicity, miR-122 increased in kidney tubular cells; this was abolished in Dicer-CKO mice. Depletion of hepatocyte microRNAs increased expression and activity of the miR-122 target - cytochrome (CYP) P450 2E1 - in the kidney. Serum extracellular vesicles (ECVs) from mice with hepatotoxicity increased proximal tubular cell miR-122 and prevented cisplatin proximal tubular cell toxicity. miR-122 also increased in urinary ECVs during hepatotoxicity in humans. Transfer of microRNA was not restricted to liver injury – we detected miR-499 release with murine cardiac injury, and this correlated with an increase in the kidney. In summary, a physiological transfer of microRNA to the kidney exists, which is increased by liver injury. Regulation of renal drug response due to signalling by microRNA of hepatic origin represents a new paradigm for understanding and preventing nephrotoxicity.

scholarly journals Rho GAP myosin IXa is a regulator of kidney tubule function

2015 ◽  
Vol 309 (6) ◽  
pp. F501-F513 ◽  
Author(s):  
Sabine Thelen ◽  
Marouan Abouhamed ◽  
Giuliano Ciarimboli ◽  
Bayram Edemir ◽  
Martin Bähler
Keyword(s):  
Structural Changes ◽  
Rho Gtpase ◽  
The Body ◽  
Gtpase Activating Protein ◽  
Protein Activity ◽  
Proximal Tubule Cells ◽  
Proximal Tubular ◽  
Protein Reabsorption ◽  
Genetic Deletion ◽  
Ciliated Epithelial Cells

Mammalian class IX myosin Myo9a is a single-headed, actin-dependent motor protein with Rho GTPase-activating protein activity that negatively regulates Rho GTPase signaling. Myo9a is abundantly expressed in ciliated epithelial cells of several organs. In mice, genetic deletion of Myo9a leads to the formation of hydrocephalus. Whether Myo9a also has essential functions in the epithelia of other organs of the body has not been explored. In the present study, we report that Myo9a-deficient mice develop bilateral renal disease, characterized by dilation of proximal tubules, calyceal dilation, and thinning of the parenchyma and fibrosis. These structural changes are accompanied by polyuria (with normal vasopressin levels) and low-molecular-weight proteinuria. Immunohistochemistry revealed that Myo9a is localized to the circumferential F-actin belt of proximal tubule cells. In kidneys lacking Myo9a, the multiligand binding receptor megalin and its ligand albumin accumulated at the luminal surface of Myo9a-deficient proximal tubular cells, suggesting that endocytosis is dysregulated. In addition, we found, surprisingly, that levels of murine diaphanous-related formin-1, a Rho effector, were decreased in Myo9a-deficient kidneys as well as in Myo9a knockdown LLC-PK1 cells. In summary, deletion of the Rho GTPase-activating protein Myo9a in mice causes proximal tubular dilation and fibrosis, and we speculate that downregulation of murine diaphanous-related formin-1 and impaired protein reabsorption contribute to the pathophysiology.

Effect of Exercise on the Renal Clearance of Amylase and Lysozyme in Humans

1972 ◽  
Vol 43 (1) ◽  
pp. 115-120 ◽  
Author(s):  
J. R. Poortmans
Keyword(s):  
Renal Clearance ◽  
Total Protein ◽  
Strenuous Exercise ◽  
Protein Excretion ◽  
Before And After ◽  
Proximal Tubular ◽  
Protein Reabsorption ◽  
Proximal Tubular Function ◽  
Very High ◽  
Serum And Urine

1. Total protein amount and amylase and lysozyme activities were measured in the serum and urine of healthy women and men before and after strenuous exercise. 2. Exercise produced no major difference in the serum activities of amylase and lysozyme. 3. The renal clearance of amylase was unaffected by strenuous exercise, but total protein excretion was markedly increased. 4. Very high values of renal clearance of lysozyme were observed after exercise. This implies that the proximal tubular function of protein reabsorption was specifically affected.

scholarly journals Antiproteinuric Therapy while Preventing the Abnormal Protein Traffic in Proximal Tubule Abrogates Protein- and Complement-Dependent Interstitial Inflammation in Experimental Renal Disease

1999 ◽  
Vol 10 (4) ◽  
pp. 804-813
Author(s):  
MAURO ABBATE ◽  
CARLA ZOJA ◽  
DANIELA ROTTOLI ◽  
DANIELA CORNA ◽  
NORBERTO PERICO ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Proximal Tubules ◽  
Complement C3 ◽  
Abnormal Protein ◽  
Protein Traffic ◽  
Tubular Cells ◽  
Mhc Ii ◽  
Interstitial Inflammation ◽  
Proximal Tubular ◽  
Protein Reabsorption

Abstract. In proteinuric glomerulopathies, the excess traffic of proteins into the renal tubule is a candidate trigger of interstitial inflammatory and immune events leading to progressive injury, and a key target for the renoprotective action of antiproteinuric drugs. Among proteins trafficked to the proximal tubule, the third component of complement (C3) can be activated locally and contribute to inflammation at sites of protein reabsorption. Experiments were performed in rats with renal mass reduction (RMR, 5/6 nephrectomy) with the following aims: (1) to study Ig (IgG) and complement deposition in proximal tubules, and interstitial macrophage infiltration and MHC class II expression at intervals after surgery by double immunofluorescence analysis; (2) to assess whether lisinopril (angiotensin-converting enzyme inhibitor [ACEi], 25 mg/L in the drinking water, from either day 1 or day 7) limited IgG and C3 accumulation and interstitial inflammation at day 30. In 7-d remnant kidneys, intracellular staining for both IgG and C3 was detectable in proximal tubules in focal areas; C3 was restricted to IgG-positive tubular cells, and there were no interstitial ED-1 macrophage and MHC II-positive cellular infiltrates. In 14-d and 30-d remnant kidneys, proximal tubular IgG and C3 staining was associated with the appearance of interstitial infiltrates that preferentially localized to areas of tubules positive for both proteins. RMR rats given ACEi had no or limited increases in levels of urinary protein excretion, tubular IgG, and C3 reactivity, and interstitial cellular infiltrates in kidneys at 30 d, even when ACEi was started from day 7 after surgery. These findings document that (1) in RMR, IgG and C3 accumulation in proximal tubular cells is followed by leukocyte infiltration and MHC II overexpression in the adjacent interstitium; (2) ACEi while preventing proteinuria limits both tubular accumulation of IgG and C3 and interstitial inflammation. The data suggest that ACE inhibition can be renoprotective by limiting the early abnormal protein traffic in proximal tubule and consequent deleterious effects of excess protein reabsorption, including the accumulation and local activation of complement as well as the induction of chemokines and endothelin genes known to promote interstitial inflammation and fibrosis.

NHE3 Na+/H+ exchanger supports proximal tubular protein reabsorption in vivo

2004 ◽  
Vol 287 (3) ◽  
pp. F469-F473 ◽  
Author(s):  
Michael Gekle ◽  
Katharina Völker ◽  
Sigrid Mildenberger ◽  
Ruth Freudinger ◽  
Gary E. Shull ◽  
...  
Keyword(s):  
Ph Homeostasis ◽  
Genetic Studies ◽  
Opossum Kidney ◽  
Protein Excretion ◽  
Opossum Kidney Cells ◽  
Sds Page ◽  
Proximal Tubular ◽  
Protein Reabsorption ◽  
Endosomal Ph

Proximal tubular receptor-mediated endocytosis (RME) of filtered proteins prevents proteinuria. Pharmacological and genetic studies in cultured opossum kidney cells have shown that the apical Na+/H+ exchanger isoform 3 (NHE3) supports RME by interference with endosomal pH homeostasis and endocytic fusion events. However, it is not known whether NHE3 also supports proximal tubular RME in vivo. We analyzed proximal tubular protein reabsorption by microinfusion experiments in rats and investigated renal protein excretion in NHE3 knockout (Nhe3 −/−) mice. Inhibition of NHE3 by EIPA or S-3226 reduced the fractional reabsorption of [14C]cytochrome c by ∼50% during early proximal microinfusion. During early distal microinfusion, no protein reabsorption could be detected. Urinary protein excretion of Nhe3 −/− or heterozygous mutant mice was significantly higher compared with wild-type mice. SDS-PAGE analysis of urinary proteins revealed that Nhe3 −/− animals excreted proteins the size of albumin or smaller. Thus a reduction in NHE3 activity or abundance causes tubular proteinuria. These data show that NHE3 supports proximal tubular RME of filtered proteins in vivo.

scholarly journals Axial differences in endocytosis along the kidney proximal tubule

2019 ◽  
Vol 317 (6) ◽  
pp. F1526-F1530 ◽  
Author(s):  
Marcello Polesel ◽  
Andrew M. Hall
Keyword(s):  
Proximal Tubule ◽  
High Capacity ◽  
Fluid Phase ◽  
Imaging Studies ◽  
Protein Uptake ◽  
Disease States ◽  
Proximal Tubular ◽  
Protein Reabsorption ◽  
Proximal Tubular Function ◽  
Very High

The proximal tubule (PT) reabsorbs filtered proteins via receptor-mediated endocytosis to prevent energetically inefficient wasting in the urine. Recent intravital imaging studies have suggested that protein reabsorption occurs in early (S1) segments, which have a very high capacity. In contrast, uptake of fluid phase substrates also occurs in distal (S2) segments. In this article, we will review these findings and their implications for understanding integrated proximal tubular function, patterns of damage caused by endocytosed toxins, and the origins of proteinuria. We will also discuss whether compensatory downstream increases in protein uptake might occur in disease states, and the environmental factors that could drive these changes.

Effects of Steroids on Fetal Rat Liver

1969 ◽  
Vol 27 ◽  
pp. 350-351
Author(s):  
F. G. Zaki
Keyword(s):  
Liver Injury ◽  
Rat Liver ◽  
Fetal Liver ◽  
Dosage Level ◽  
Maternal Plasma ◽  
Methyl Prednisolone ◽  
Fetal Rat ◽  
Toxic Agents ◽  
Fetal Rat Liver ◽  
Neonatal Liver

Fetal and neonatal liver injury induced by agents circulating in maternal plasma, even though well recognized, its morphological manifestations are not yet established. As part of our studies of fetal and neonatal liver injury induced by maternal nutritional disorders, metabolic impairment and toxic agents, the effects of two anti-inflammatory steroids have been recently inves tigated.Triamcinolone and methyl prednisolone were injected each in a group of rats during pregnancy at a-dosage level of 2 mgm three times a week. Fetal liver was studied at 18 days of gestation. Litter size and weight markedly decreased than those of control rats. Stillbirths and resorption were of higher incidence in the triamcinolone group than in those given the prednisolone.

Sign in / Sign up

Export Citation Format

Share Document