“…The endocytosed crystals were transported to the lysosome and dissolved by hydrolytic enzymes, 11 thereby reducing the number of crystals adhering to the cell surface (Figures 5 and 6) and reducing the risk of kidney stone formation. 42 Chaiyarit et al 11 showed that the micron-sized COM crystals were incubated with MDCK for 1 h, and the amount of internalized crystals reached 14.83% ± 0.85%. After internalization for 16 h, the size of the internalized crystals gradually decreased with time, indicating that COM crystals were dissolved in the lysosome of MDCK cells.…”
Section: Discussionmentioning
confidence: 99%
“…The endocytosis ability of damaged cells to nano-COM was significantly lower than that of normal cells (Figure B); meanwhile, the uptake ability for COM significantly increased after the PYP repair. The endocytosed crystals were transported to the lysosome and dissolved by hydrolytic enzymes, thereby reducing the number of crystals adhering to the cell surface (Figures and ) and reducing the risk of kidney stone formation . Chaiyarit et al showed that the micron-sized COM crystals were incubated with MDCK for 1 h, and the amount of internalized crystals reached 14.83% ± 0.85%.…”
The adhesion and endocytosis of renal epithelial cells to urinary microcrystals are closely related to kidney stone formation; however, the mechanism of cell state changes that affect adhesion and endocytosis remains unclear. In this study, a damaged cell model was established using oxalate to impair human kidney proximal tubular epithelial cells (HK-2). Then, we used four degraded Porphyra yezoensis polysaccharides (PYPs), namely, PYP1, PYP2, PYP3, and PYP4, with molecular weight of 576.2, 49.5, 12.6, and 4.02 kDa, respectively, to repair the damaged cells. After repairing the damaged HK-2 cells by PYPs, the cell morphology gradually recovered to near normal; the cell migration speed increased; the phosphatidylserine eversion ratio and osteopontin expression decreased; and the intracellular adenosine triphosphate was promoted. The adhesion and endocytosis of calcium oxalate monohydrate (COM) crystals were closely related to cell state. Normal cells could endocytose crystals more than the damaged cells, whereas damaged cells could adhere to crystals more than the normal cells. The cells repaired by PYPs inhibited the adhesion of nano-COM crystals and promoted the endocytosis of the adherent crystals, thereby reducing the adhesion of crystals on the cell surface under both effects. As the molecular weight of PYP decreased, the ability of PYP to repair cells, inhibit crystal adhesion, and promote endocytosis of cells was enhanced; that is, PYP4, which had the lowest molecular weight, exhibited the best biological activity. Therefore, PYPs, especially PYP4, may become an optional green drug to inhibit the formation and recurrence of calcium oxalate stones.
“…The endocytosed crystals were transported to the lysosome and dissolved by hydrolytic enzymes, 11 thereby reducing the number of crystals adhering to the cell surface (Figures 5 and 6) and reducing the risk of kidney stone formation. 42 Chaiyarit et al 11 showed that the micron-sized COM crystals were incubated with MDCK for 1 h, and the amount of internalized crystals reached 14.83% ± 0.85%. After internalization for 16 h, the size of the internalized crystals gradually decreased with time, indicating that COM crystals were dissolved in the lysosome of MDCK cells.…”
Section: Discussionmentioning
confidence: 99%
“…The endocytosis ability of damaged cells to nano-COM was significantly lower than that of normal cells (Figure B); meanwhile, the uptake ability for COM significantly increased after the PYP repair. The endocytosed crystals were transported to the lysosome and dissolved by hydrolytic enzymes, thereby reducing the number of crystals adhering to the cell surface (Figures and ) and reducing the risk of kidney stone formation . Chaiyarit et al showed that the micron-sized COM crystals were incubated with MDCK for 1 h, and the amount of internalized crystals reached 14.83% ± 0.85%.…”
The adhesion and endocytosis of renal epithelial cells to urinary microcrystals are closely related to kidney stone formation; however, the mechanism of cell state changes that affect adhesion and endocytosis remains unclear. In this study, a damaged cell model was established using oxalate to impair human kidney proximal tubular epithelial cells (HK-2). Then, we used four degraded Porphyra yezoensis polysaccharides (PYPs), namely, PYP1, PYP2, PYP3, and PYP4, with molecular weight of 576.2, 49.5, 12.6, and 4.02 kDa, respectively, to repair the damaged cells. After repairing the damaged HK-2 cells by PYPs, the cell morphology gradually recovered to near normal; the cell migration speed increased; the phosphatidylserine eversion ratio and osteopontin expression decreased; and the intracellular adenosine triphosphate was promoted. The adhesion and endocytosis of calcium oxalate monohydrate (COM) crystals were closely related to cell state. Normal cells could endocytose crystals more than the damaged cells, whereas damaged cells could adhere to crystals more than the normal cells. The cells repaired by PYPs inhibited the adhesion of nano-COM crystals and promoted the endocytosis of the adherent crystals, thereby reducing the adhesion of crystals on the cell surface under both effects. As the molecular weight of PYP decreased, the ability of PYP to repair cells, inhibit crystal adhesion, and promote endocytosis of cells was enhanced; that is, PYP4, which had the lowest molecular weight, exhibited the best biological activity. Therefore, PYPs, especially PYP4, may become an optional green drug to inhibit the formation and recurrence of calcium oxalate stones.
“…In this regard, transient hyperuricosuria is not uncommon in healthy men, and in serial determinations may occur approximately 20% of the time [64]. While most attention has focused on the effects of urate crystalluria as a nephrotoxin [65], [66], uricosuria in the absence of crystalluria may also affect tubular function [67], [68], [69], [70] by inducing oxidative stress, epithelial-mesenchymal transformation and tubular production of chemotactic factors, and by altering cell proliferation [67], [68], [70], [71], [72].Fig. 1Postulated mechanisms for uric acid induced acute kidney injury.…”
Section: Uric Acid In Acute Kidney Injurymentioning
“…Soluble UA may have direct pro-inflammatory effects as shown by previous studies, including stimulating the production of C-reactive protein (CRP) and monocyte chemotactic protein-1 (MCP-1) in vascular cells through the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) (11,12), inducing endothelial dysfunction with mitochondrial alterations and decreased intracellular adenosine triphosphate (ATP) concentrations (13), exerting pro-oxidative effects mediated in part by the activation of the lactaldehyde reductase (NADPH) oxidase system and stimulating mitochondrial oxidative stress in vascular cells or adipocytes (14). In the kidneys, observational studies have also observed renal injuries induced by soluble UA without urate crystal formation induced by inflammation (15)(16)(17)(18). In clinical observations, not only hyperuricemia, but also a higher normal level of UA has been shown to increase the risk of the early progression of renal function loss in patients with type 1 diabetes (19).…”
Urate crystals activate innate immunity through Toll like receptor 4 (TLR4) activation, leading to the formation of the NACHT, LRR and PYD domains-containing protein 3 [NALP3; also known as NOD-like receptor family, pyrin domain containing 3 (NALP3) and cryopyrin] inflammasome, caspase-1 activation and interleukin (IL)-1β expression in gout. However, whether elevated serum uric acid (UA) levels are associated with the development and progression of renal diseases without renal urate crystal deposition remains unknown. In the present study, human primary renal proximal tubule epithelial cells were incubated with soluble UA (100 µg/ml) with or without the TLR4 inhibitor, TAK242 (1 µM). The gene expression and protein synthesis of TLR4, NALP3, caspase-1, IL-1β and intercellular adhesion molecule-1 (ICAM-1) were detected by real-time PCR, ELISA, western blot analysis and fluorescence-activated cell sorting (FACS), respectively. Soluble UA significantly enhanced TLR4, NALP3, caspase-1, IL-1β and ICAM-1 expression in the human primary renal proximal tubule epithelial cells. The TLR4 inhibitor, TAK242 effectively blocked the soluble UA-induced upregulation of TLR4, NALP3, caspase-1, IL-1β and ICAM-1 expression in the human primary renal proximal tubule epithelial cells. Our findings indicate that soluble UA enhances NALP3 expression, caspase-1 activation, IL-1β and ICAM-1 production in renal proximal tubule epithelial cells in a TLR4-dependent manner, suggesting the activation of innate immunity in human primary renal proximal tubule epithelial cells by soluble UA.
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