scholarly journals The Activation of ROS/NF-κB/MMP-9 Pathway Promotes Calcium-Induced Kidney Crystal Deposition

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Yue Wu ◽  
Jiaqiao Zhang ◽  
Cong Li ◽  
Henglong Hu ◽  
Baolong Qin ◽  
...  
Keyword(s):  
Stone Formation ◽  
Rat Kidney ◽  
Idiopathic Hypercalciuria ◽  
Renal Tubules ◽  
Sprague Dawley ◽  
High Concentration ◽  
Crystal Deposition ◽  
Ectopic Tissue ◽  
High Calcium ◽  
Related Proteins

Idiopathic hypercalciuria is an important risk factor for the formation of calcium-containing kidney stones. Matrix metalloproteinase-9 (MMP-9) is closely related to cell and tissue remodeling and is involved in ectopic tissue calcification. However, little is known about its role in kidney stone formation. In this study, we found that the expression of MMP-9 and that of osteoblastic-related proteins was increased in normal rat kidney epithelial-like (NRK-52E) cells following treatment with a high concentration of calcium, while the knockout or overexpression of MMP-9 could, respectively, significantly inhibit or upregulate the expression of osteoblastic-related proteins and calcium crystal deposition. In addition, apoptosis and calcium crystal deposition were significantly reduced in Sprague–Dawley rats with 1,25(OH)2D3-induced hypercalciuria following MMP-9 inhibitor I treatment. Furthermore, inhibiting reactive oxygen species (ROS) production or the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway significantly reduced calcium-induced MMP-9 expression and calcium crystal deposition. In summary, our results suggested that a high calcium concentration promotes epithelial–osteoblastic transformation and calcium crystal deposition in renal tubule cells by regulating the ROS/NF-κB/MMP-9 axis and identified a novel role for MMP-9 in regulating calcium-induced calcium crystal deposition in renal tubules.

Ontogeny of glycine transport in isolated rat renal tubules

1977 ◽  
Vol 233 (3) ◽  
pp. F241-F246
Author(s):  
K. S. Roth ◽  
S. M. Hwang ◽  
J. W. London ◽  
S. Segal
Keyword(s):  
Rat Kidney ◽  
Renal Tubules ◽  
Sprague Dawley ◽  
Entry Rate ◽  
Glycine Uptake ◽  
Adult Rat ◽  
High Affinity ◽  
Sprague Dawley Rats ◽  
Rate Kinetics ◽  
Isolated Renal Tubule

Isolated renal tubule preparations were made from newborn Sprague-Dawley rats and used to study initial entry rate kinetics of glycine. The results were compared to those obtained in the isolated tubule preparation from the adult rat kidney. While initial rates of glycine uptake were identical for newborn and adult tubules, significant differences in influx kinetics were demonstrated. Of the two apparent transport Km systems shown to be present in the newborn tubule, the high-affinity, low-capacity system accounts for about 40% of total glycine uptake at physiologic concentrations. The high-affinity, low-capacity system of the adult tissue accounts for about 10% of total uptake at the same concentration range. The data lend strength to the argument against the concept that the physiologic hyperglycinuria of the newborn rat is due to either impaired ability to concentrate glycine intracellularly or to absence of one or more transport mechanisms for glycine.

scholarly journals Crystalline Nephropathies

2012 ◽  
Vol 136 (7) ◽  
pp. 713-720 ◽  
Author(s):  
Leal C. Herlitz ◽  
Vivette D. D'Agati ◽  
Glen S. Markowitz
Keyword(s):  
Hematologic Malignancy ◽  
High Volume ◽  
Practical Experience ◽  
Renal Tubules ◽  
High Concentration ◽  
Drug Induced ◽  
Accurate Identification ◽  
Pathology Laboratory ◽  
Crystal Deposition ◽  
Concentration Of Ions

Context.—The kidney is a favored site for crystal deposition because of the high concentration of ions and molecules reached at the level of the renal tubules in the course of filtration. This review focuses on crystalline nephropathies in 4 broad categories: (1) dysproteinemia- associated, (2) drug-induced, (3) calcium-containing, and (4) metabolic or genetic. Objective.—To provide a framework for accurate identification of the diverse types of crystals encountered in the kidney in order to formulate an appropriate differential diagnosis and guide additional testing and treatment. Data Sources.—Review of pertinent published literature along with practical experience gained in a high-volume renal pathology laboratory. Conclusions.—Accurate identification of crystals encountered in the kidney is essential in detecting conditions ranging from hematologic malignancy to drug toxicity to metabolic disorders. Detailed clinical-pathologic correlation is needed to accurately diagnose the underlying cause of most crystalline nephropathies.

Monoaminergic innervation of the rat kidney: a quantitative study

1990 ◽  
Vol 259 (3) ◽  
pp. F503-F511 ◽  
Author(s):  
L. Barajas ◽  
K. Powers
Keyword(s):  
Collecting Duct ◽  
Rat Kidney ◽  
Sympathetic Innervation ◽  
Renal Tubules ◽  
Vascular Bundles ◽  
Thick Ascending Limb ◽  
High Concentration ◽  
Renal Vasculature ◽  
Indirect Measure ◽  
Afferent Arterioles

The sympathetic innervation of the renal tubules and vasculature was characterized by measuring the overlap of accumulations of autoradiographic grains (AAGs) on these structures in autoradiograms of kidney sections from rats injected with tritiated norepinephrine. AAG overlap was used as an indirect measure of the innervation of those structures. The renal vasculature showed x 4.5 more AAG overlap than observed on renal tubules. The greatest amount of AAG overlap occurred on afferent arterioles, followed by efferent arterioles, interlobular arteries, cortical capillaries, arcuate arteries, and renal veins. High concentration of AAGs occurred along the vascular bundles of the outer stripe. In the tubular nephron the proximal tubule had the greatest amount of AAG overlap, followed by the cortical thick ascending limb of Henle, the connecting tubule, the distal convoluted tubule, and the collecting duct. It was found that afferent arterioles had significantly higher mean density of AAG overlap than efferent arterioles for the superficial, midcortical, and juxtamedullary (vascular bundles excluded) renal cortex. There was consistently more AAG perimeter facing the interstitium than overlapping the vasculature. These observations, together with the ultrastructural distribution of synaptic vesicles in varicosities, suggest that the interstitium might be an additional pathway of neurotransmitter access to the effector structures.

Involvement of Cellular Membranes and their Lipids in Nucleation of Stone Forming Crystals

1999 ◽  
Vol 599 ◽  
Author(s):  
S. R. Khan ◽  
J. M. Fasano ◽  
R. Backov ◽  
D. R. Talham
Keyword(s):  
Calcium Phosphate ◽  
Calcium Oxalate ◽  
Kidney Stones ◽  
Membrane Lipids ◽  
Stone Formation ◽  
Rat Kidney ◽  
Langmuir Monolayers ◽  
Membrane Vesicles ◽  
In Vivo Studies ◽  
Renal Tubules

AbstractMore than 80% of human kidney stones consist of calcium oxalate and/or calcium phosphate. Human urine is generally metastable with respect to these salts and their nucleation is heterogeneous. Based on: 1. ultrastructural and immunohistochemical studies of stones in which cellular degradation products and lipids were commonly seen in association with calcific crystals and 2. in vivo studies of nephrolithiasis in rat models where calcium oxalate (CaOx) and calcium phosphate (CaP) crystals almost always formed and seen in association with cell membranes, we proposed that membranes and their lipids are involved in crystallization of these salts. To test our hypothesis we isolated organic matrix of kidney stones, its lipid contents and membrane vesicles from epithelial cells of rat kidney and incubated them in metastable solution of CaOx. Both membrane vesicles and matrix from the stones supported crystallization of CaOx and crystals formed in association with the membranes. Lipids of the stone matrix appeared better nucleators than whole matrix. Urine spends only minutes within the kidneys thus any nucleation which can lead to stone formation has to occur rapidly. In studies described here, we demonstrate that under specific circumstances relevant to conditions in the kidney, membrane vesicle- supported CaOx crystallization can occur within seconds, demonstrating the possibility of such events happening in the kidneys. We also studied CaOx monohydrate (COM) precipitation at Langmuir monolayers of dipalmitoylphosphatidylglecerol (DPPG), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS) showed precipitation to be heterogeneous and selective with a majority of crystals orienting with the 101 face of COM facing the monolayer. Our results show that membrane lipids can initiate nucleation of calcium oxalate crystals in solutions similar to those present in the kidneys. In addition these crystals form within the time urine spends inside the renal tubules demonstrating for the first time the likelihood of occurrence of such a phenomenon in the kidneys during stone formation.

scholarly journals Immortalization and Characterization of Rat Lingual Keratinocytes in a High-Calcium and Feeder-Free Culture System Using ROCK Inhibitor Y-27632

2021 ◽  
Vol 22 (13) ◽  
pp. 6782
Author(s):  
Zixing Chen ◽  
Wenmeng He ◽  
Thomas Chun Ning Leung ◽  
Hau Yin Chung
Keyword(s):  
Calcium Imaging ◽  
Cultured Cells ◽  
Rho Kinase ◽  
Culture Method ◽  
Taste Bud ◽  
Label Free ◽  
Sprague Dawley ◽  
Rock Inhibitor ◽  
High Calcium

Cultured keratinocytes are desirable models for biological and medical studies. However, primary keratinocytes are difficult to maintain, and there has been little research on lingual keratinocyte culture. Here, we investigated the effect of Y-27632, a Rho kinase (ROCK) inhibitor, on the immortalization and characterization of cultured rat lingual keratinocyte (RLKs). Three Y-27632–supplemented media were screened for the cultivation of RLKs isolated from Sprague–Dawley rats. Phalloidin staining and TUNEL assay were applied to visualize cytoskeleton dynamics and cell apoptosis following Y-27632 removal. Label-free proteomics, RT-PCR, calcium imaging, and cytogenetic studies were conducted to characterize the cultured cells. Results showed that RLKs could be conditionally immortalized in a high-calcium medium in the absence of feeder cells, although they did not exhibit normal karyotypes. The removal of Y-27632 from the culture medium led to reversible cytoskeletal reorganization and nuclear enlargement without triggering apoptosis, and a total of 239 differentially expressed proteins were identified by proteomic analysis. Notably, RLKs derived from the non-taste epithelium expressed some molecular markers characteristic of taste bud cells, yet calcium imaging revealed that they rarely responded to tastants. Collectively, we established a high-calcium and feeder-free culture method for the long-term maintenance of RLKs. Our results shed some new light on the immortalization and differentiation of lingual keratinocytes.

Does Crystal Deposition in Genetic Hypercalciuric Rat Kidney Tissue Share Similarities With Bone Formation?

Urology ◽  
2014 ◽  
Vol 83 (2) ◽  
pp. 509.e7-509.e14 ◽  
Author(s):  
Zhaohui Jia ◽  
Shaogang Wang ◽  
Jinhui Tang ◽  
Deng He ◽  
Lei Cui ◽  
...  
Keyword(s):  
Bone Formation ◽  
Rat Kidney ◽  
Kidney Tissue ◽  
Crystal Deposition

Parathyroid Hormone- and Deoxycorticosterone Acetate-Induced Hypertension in the Rat

1980 ◽  
Vol 58 (5) ◽  
pp. 365-371 ◽  
Author(s):  
A. Berthelot ◽  
A. Gairard
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Secretion ◽  
Sprague Dawley ◽  
Physiological Concentration ◽  
Deoxycorticosterone Acetate ◽  
Calcium Diet ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
High Calcium ◽  
High Calcium Diet

1. Hypertension induced by treatment with deoxycorticosterone acetate and sodium chloride was studied in male Sprague-Dawley rats and related to parathyroid hormone secretion. 2. Lack of parathyroid hormone (due to parathyroidectomy) or decreased parathormone secretion (due to a high-calcium diet) partially inhibited the development of arterial hypertension. 3. In contrast, in thyroparathyroidectomized rats supplemented with thyroxine, the administration of parathyroid hormone rapidly elevated arterial blood pressure. 4. Maintaining a physiological concentration of serum calcium in the absence of parathyroid hormone (by feeding a high-calcium diet to parathyroidectomized rats) was not sufficient to establish mineralocorticoid hypertension. 5. These results show that parathyroid hormone is necessary for the complete development of mineralocorticoid hypertension.

Sepsis induces changes in the expression and distribution of Toll-like receptor 4 in the rat kidney

2006 ◽  
Vol 290 (5) ◽  
pp. F1034-F1043 ◽  
Author(s):  
Tarek M. El-Achkar ◽  
Xiaoping Huang ◽  
Zoya Plotkin ◽  
Ruben M. Sandoval ◽  
Georges J. Rhodes ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Expression Patterns ◽  
Cecal Ligation ◽  
Proximal Tubules ◽  
Microbial Pathogens ◽  
Sprague Dawley ◽  
Renal Vasculature ◽  
Two Photon Microscopy ◽  
Sprague Dawley Rats ◽  
Cellular Signal

Toll-like receptors (TLRs) are now recognized as the major receptors for microbial pathogens on cells of the innate immune system. Recently, TLRs were also identified in many organs including the kidney. However, the cellular distribution and role of these renal TLRs remain largely unknown. In this paper, we investigated the expression of TLR4 in a cecal ligation and puncture (CLP) model of sepsis in Sprague-Dawley rats utilizing fluorescence microscopy. In sham animals, TLR4 was expressed predominantly in Tamm-Horsfall protein (THP)-positive tubules. In CLP animals, TLR4 expression increased markedly in all tubules (proximal and distal), glomeruli, and the renal vasculature. The staining showed a strong apical distribution in all tubules. A moderately less intense cellular signal colocalized partially with the Golgi apparatus. In addition, kidneys from septic rats showed increased expression of CD14 and THP. They each colocalized strongly with TLR4, albeit in different tubular segments. We also imaged the kidneys of live septic animals with two-photon microscopy after fluorescent lipopolysaccharide (LPS) injection. Within 10 min, LPS was seen at the brush border of some proximal tubules. Within 60 min, LPS was fully cytoplasmic in proximal tubules. Conversely, distal tubules showed no LPS uptake. We conclude that TLR4, CD14, and THP have specific renal cellular and tubular expression patterns that are markedly affected by sepsis. Systemic endotoxin can freely access the tubular and cellular sites where these proteins are present. Therefore, locally expressed TLRs and other interacting proteins could potentially modulate the renal response to systemic sepsis.

Angiotensin II Ca2+ signaling in rat afferent arterioles: stimulation of cyclic ADP ribose and IP3 pathways

2005 ◽  
Vol 288 (4) ◽  
pp. F785-F791 ◽  
Author(s):  
Susan K. Fellner ◽  
William J. Arendshorst
Keyword(s):  
Calcium Release ◽  
Rat Kidney ◽  
Ang Ii ◽  
High Concentration ◽  
Inositol Trisphosphate Receptor ◽  
Cyclic Adp Ribose ◽  
Specific Antagonist ◽  
Afferent Arterioles ◽  
Trisphosphate Receptor ◽  
Calcium Induced Calcium Release

ANG II induces a rise in cytosolic Ca2+ ([Ca2+]i) in vascular smooth muscle (VSM) cells via inositol trisphosphate receptor (IP3R) activation and release of Ca2+ from the sarcoplasmic reticulum (SR). The Ca2+ signal is augmented by calcium-induced calcium release (CICR) and by cyclic adeninediphosphate ribose (cADPR), which sensitizes the ryanodine-sensitive receptor (RyR) to Ca2+ to further amplify CICR. cADPR is synthesized from β-nicotinamide adenine dinucleotide (NAD+) by a membrane-bound bifunctional enzyme, ADPR cyclase. To investigate the possibility that ANG II activates the ADPR cyclase of afferent arterioles, we used inhibitors of the IP3R, RyR, and ADPR cyclase. Afferent arterioles were isolated from rat kidney with the magnetized microsphere and sieving technique and loaded with fura-2 to measure [Ca2+]i. In Ca2+-containing buffer, ANG II increased [Ca2+]i by 125 ± 10 nM. In the presence of the IP3R antagonists TMB-8 and 2-APB, the peak responses to ANG II were reduced by 74 and 81%, respectively. The specific antagonist of cADPR 8-Br ADPR and a high concentration of ryanodine (100 μM) inhibited the ANG II-induced increases in [Ca2+]i by 75 and 69%, respectively. Nicotinamide and Zn2+ are known inhibitors of the VSM ADPR cyclase. Nicotinamide diminished the [Ca2+]i response to ANG II by 66%. In calcium-free buffer, Zn2+ reduced the ANG II response by 68%. Simultaneous blockade of the IP3 and cADPR pathways diminished the [Ca2+]i response to ANG II by 83%. We conclude that ANG II initiates Ca2+ mobilization from the SR in afferent arterioles via the classic IP3R pathway and that ANG II may lead to activation of the ADPR cyclase to form cADPR, which, via its action on the RyR, substantially augments the Ca2+ response.

INHIBITORY ACTION OF CALCIUM ON THE INACTIVATION OF ANTIDIURETIC HORMONE BY RAT KIDNEY SLICES

1963 ◽  
Vol 44 (4) ◽  
pp. 563-569 ◽  
Author(s):  
N. A. Thorn ◽  
N. B. S. Willumsen
Keyword(s):  
Arginine Vasopressin ◽  
Inhibitory Action ◽  
Calcium Concentration ◽  
Rat Kidney ◽  
Kidney Medulla ◽  
Marked Inhibition ◽  
High Calcium ◽  
Rational Explanation ◽  
High Calcium Concentration ◽  
Cellular Permeability

ABSTRACT Increasing the calcium concentration 5 times or more in the medium used for studying the inactivation of arginine-vasopressin by rat kidney medulla slices caused a marked inhibition of the inactivating activity of such slices. This effect was not found in homogenates of rat kidney medulla. The results are in agreement with the interpretation that the high calcium concentration decreased the cellular permeability to the hormone. This would seem to give a rational explanation of the vasopressin-resistant diabetes insipidus which is found in hypercalcaemia.

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