Comparison of the adhesion and endocytosis of calcium oxalate dihydrate to HK-2 cells before and after repair by Astragalus polysaccharide

Abstract

This work investigated the effects of repairing injured renal proximal tubular epithelial (HK-2) cells by using three Astragalus polysaccharides (APS) with different molecular weights and the adhesion and endocytosis of HK-2 cells to the calcium oxalate dihydrate (COD) nanocrystals before and after repair to develop new products that can protect against kidney stones. HK-2 cells cultured in vitro were injured with 2.6 mmol/L oxalic acid to establish a damaged cell model. Three kinds of APS (APS0, APS1, and APS2 with molecular weights of 11.03, 4.72, and 2.60 kDa, respectively) were used to repair the damaged cells. The changes in the adhesion and endocytosis of 100 nm COD crystals to cells before and after the repair were detected. After the repair of HK-2 cells by the APS, the speed of wound healing of the damaged HK-2 cells increased, and the amount of phosphatidylserine (PS) ectropion decreased. In addition, the proportion of cells with adhered COD crystals decreased, whereas the proportion of cells with internalized crystals increased. As a result of the repair activity, APS can inhibit the adhesion and promote the endocytosis of COD nanocrystals to damaged cells. APS1, which had a moderate molecular weight, displayed the strongest abilities to repair the cells, inhibit adhesion, and promote endocytosis. Thus, APS, particularly APS1, may serve as potential green drugs for preventing kidney stones.

Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury

“…The mortality rate of AKI patients caused by sepsis is more than 70%, which is significantly higher than that of sepsis patients without AKI [ 19 ]. It has been reported that sepsis-induced AKI exhibits significant inflammatory response-mediated damage and is accompanied by significant apoptosis [ 20 ]. In this study, we first confirmed through experiments in mice that APS can inhibit AKI damage caused by LPS, can reduce the concentrations of BUN and SCr, and can reduce the levels of TNF- α and IL-1 β .…”

“…It has been proven by research and clinical evidence that it has various pharmacological activities such as anti-inflammatory, antitumor, antidiabetic, antiviral, hepatoprotective, antiatherosclerosis, hematopoiesis, and neuroprotection [ 13 ]. In kidney disease, APS has been found to prevent cisplatin-induced AKI by reducing oxidative damage and antiapoptosis [ 17 ] and preventing kidney stones by repairing cells, inhibiting adhesion, and promoting endocytosis [ 20 ]. Studies have reported that the protective effect of APS on organs may be related to its anti-inflammatory activity [ 13 , 17 ].…”

Increased Sulfation in Gracilaria fisheri Sulfated Galactans Enhances Antioxidant and Antiurolithiatic Activities and Protects HK-2 Cell Death Induced by Sodium Oxalate

“…In addition, L-SG was less effective than both N-SG and S-SG, although it has been reported that low molecular weight polysaccharides exhibit better absorption and bioavailability [29]. However, the biological activity of these polysaccharides could be reduced due to their being less likely to form a biologically active polymeric structure [30].…”

Resveratrol inhibits calcium oxalate crystal growth, reduces adhesion to renal cells and induces crystal internalization into the cells, but promotes crystal aggregation

“…Several previous studies have investigated the ability of renal cells to engulf or endocytose CaOx crystals ( Chaiyarit et al, 2016 ; Han et al, 2019 ; Kanlaya et al, 2013 ; Lieske and Deganello, 1999 ; Lieske et al, 1997 ; Schepers et al, 2003 ). Among various endocytic mechanisms, previous evidence has revealed that macropinocytosis is the major mechanism for CaOx internalization into renal epithelial cells ( Kanlaya et al, 2013 ).…”