Systematic evaluation for effects of urine pH on calcium oxalate crystallization, crystal-cell adhesion and internalization into renal tubular cells

Manissorn, Juthatip; Fong-ngern, Kedsarin; Peerapen, Paleerath; Thongboonkerd, Visith

doi:10.1038/s41598-017-01953-4

Cited by 91 publications

(62 citation statements)

References 51 publications

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“…Calcium oxalate (CaOx) is the most common type of kidney stones, up to 75–90%, and the recurrence rate is approximately 50% within 10 years . The supersaturation, nucleation, growth, aggregation to crystals followed by direct adhesion on renal tubular epithelial cells is the general process of CaOx stones formation in the kidney, further leading to pain, urinary tract infections, chronic renal disease, and even loss of kidney function . However, the definite mechanisms regarding how and when CaOx stones damage kidney remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

Chen

Wei

Meng

et al. 2019

Part & Part Syst Charact

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Calcium oxalate (CaOx) stone is the most common type of kidney stone, with a formation process comprising supersaturation, nucleation, growth, aggregation to crystals, and adhesion on renal tubular epithelial cells. CaOx stones generally lead to renal injury; however, the underlying mechanism remains poorly understood. Accumulating evidence suggests that nanosized materials could induce much greater toxicity than bulk materials with the same components. As aggregation to nanocrystals is necessary to form CaOx stones and nanocrystals have been widely reported to elicit either prodeath or prosurvival autophagy, the aim is to address the precise role of autophagy in CaOx‐ nanocrystal‐induced cytotoxicity. Clinical CaOx stones from patients are collected followed by ball milling. As a result, CaOx nanocrystals significantly reduce renal cell viability in a dose‐ and time‐dependent manner. Further study shows that CaOx nanocrystals possess an autophagy‐inducing capacity and autophagic flux is complete. Autophagy abrogation by specific chemical inhibitor wortmannin or chloroquine obviously attenuates cytotoxicity, strongly suggesting that prodeath autophagy contributes to CaOx nanocrystals‐elicited cytotoxicity. Finally, it is revealed that autophagy is an essential signaling pathway participating in apoptosis regulation. Collectively, the findings demonstrate the role of autophagy in CaOx‐nanocrystal‐elicited cytotoxicity, and harnessing autophagy can be helpful to design promising strategies for attenuating kidney injury in nephrolithiasis.

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Section: Introductionmentioning

confidence: 99%

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

Chen

Wei

Meng

et al. 2019

Part & Part Syst Charact

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“…The treated cells were cultured in a 6-well plate. As previously described, the cells with full confluence were incubated in DMEM containing 100 µg/ml calcium oxalate monohydrate (cOM, c0350000, Sigma) for 10 min at 37̊C in a humidified atmosphere with 5% CO 2 (23). The cells were then washed by PBS twice to remove residual cOM crystals.…”

Section: Determination Of Lactate Dehydrogenase (Ldh) the Cellsmentioning

confidence: 99%

Overexpression of miR‑30c‑5p reduces cellular cytotoxicity and inhibits the formation of kidney stones through ATG5

et al. 2019

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MicroRNAs (miRNAs or miRs) are critical regulators in various diseases. In the current study, the role of miR-30c-5p in the formation of sodium oxalate-induced kidney stones was investigated. For this purpose, human renal tubular epithelial cells (HK-2 cells) were incubated with sodium oxalate at the concentrations of 100, 250, 500, 750 and 1,000 µM. cell viability and the miR-30c-5p expression level were respectively measured by ccK-8 assay and RT-qPcR. After separately transfecting miR-30c-5p mimic and inhibitor into the HK-2 cells, the cell apoptotic rate, the levels of mitochondrial membrane potential (MMP) and ROS were determined by flow cytometry. The levels of oxidative stress indicators [lactate dehydrogenase (LdH), malondialdehyde (MdA), superoxide dismutase (SOd) and catalase (cAT)] were determined using commercial kits. crystal-cell adhesion assay was performed to evaluate the crystal adhesion capacity in vitro. miR-30c-5p binding at autophagy related 5 (ATG5) was predicted by TargetScan7.2 and further verified by dual-luciferase reporter assay. Rescue experiments were performed to confirm the molecular mechanisms underlying sodium oxalate-induced kidney formation in HK-2 cells. The results revealed that sodium oxalate decreased the viability of HK-2 cells in a concentration-dependent manner, and that miR-30c-5p expression was significantly downregulated by exposure to 750 µM sodium oxalate. In addition, the increase in cell apoptosis and crystal number, and the upregulated levels of LdH, MdA and ROS were reversed by the overexpression of miR-30c-5p. Moreover, the overexpression of miR-30c-5p upregulated the levels of SOd, cAT and MMP induced by sodium oxalate. ATG5 was directly regulated by miR-30c-5p, and the inhibition of cell cytotoxicity and crystal-cell adhesion induced by miR-30c-5p mimic was blocked by ATG5. These data indicated that the overexpression of miR-30c-5p alleviated cell cytotoxicity and crystal-cell adhesion induced by sodium oxalate through ATG5. Thus, the current study provides a better understanding of the role of miR-30c-5p in sodium oxalate-induced kidney stones.

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“…Urine pH is also a very important risk factor for developing urinary stone disease. The human urine is normally slightly acidic (pH = 6.0–6.5), but it can vary between acidic (pH = 4.5) and alkaline (pH = 8.0) over a period of 24 h depending on diet, medication intake, timing or the presence of infection or disease. It has been reported that certain disorders, physiological conditions, and medication intake may increase the normal upper urine pH range to values even above pH = 8.0 .…”

Section: Introductionmentioning

confidence: 99%

“…Calcium oxalate crystallizes in three modifications: calcium oxalate monohydrate (COM, CaC 2 O 4 ·H 2 O, Whewellite), calcium oxalate dihydrate (COD, CaC 2 O 4 ·2H 2 O, Weddellite), and calcium oxalate trihydrate (COT, CaC 2 O 4 ·3H 2 O, Caoxite) . COM is the most common and thermodynamically stable (least soluble) phase and is more pathogenic for kidney stone formation because of its higher adhesive capability . COM crystallizes in the monoclinic prismatic, hexagonal, or dendrite form .…”

Section: Introductionmentioning

confidence: 99%

“…Studies in systems with elevated oxalate concentrations have shown that COM was the dominant precipitated phase, and morphology of COM was affected by the concentration and mixing of precipitation components, pH, and temperature . While calcium oxalate stones can form in acidic, neutral, and basic urine, it has been found that COM prefers precipitation in acidic and neutral, and COD in alkaline pH ranges …”

Section: Introductionmentioning

confidence: 99%

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Calcium Oxalate Precipitation in Model Systems Mimicking the Conditions of Hyperoxaluria

Stanković

Šafranko

Kontrec

et al. 2019

Crystal Research and Technology

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This work focuses on systematic research of spontaneous precipitation of calcium oxalate in model systems mimicking the chemical conditions typical for hyperoxaluria. For this purpose, model systems of three different complexities (simple, NaCl, and artificial urine system) and two initial pH (pH i = 5.0 and pH i = 9.0) at 37°C are studied. In all investigated systems, dominant precipitation of calcium oxalate monohydrate (COM) is observed, except in artificial urine system at pH i = 9.0, c i (C 2 O 4 2− ) ࣙ 6.0 mmol dm −3 and c i (Ca 2+ ) ࣙ 7.5 mmol dm −3 , where precipitation of a mixture of calcium oxalate monohydrate and calcium oxalate dihydrate occurs. The significant difference is mainly observed in COM crystal morphology. In a simple system, COM precipitates in a dendritic form; in NaCl system, dendritic form and irregular shapes are found, while in the artificial urine, prismatic hexagonal and aggregated COM crystals precipitate.

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Systematic evaluation for effects of urine pH on calcium oxalate crystallization, crystal-cell adhesion and internalization into renal tubular cells

Cited by 91 publications

References 51 publications

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

Overexpression of miR‑30c‑5p reduces cellular cytotoxicity and inhibits the formation of kidney stones through ATG5

Calcium Oxalate Precipitation in Model Systems Mimicking the Conditions of Hyperoxaluria

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