Regulatory Effects of Damaged Renal Epithelial Cells After Repair by Porphyra yezoensis Polysaccharides with Different Sulfation Degree on the Calcium Oxalate Crystal–Cell Interaction

Abstract

Background The interaction between urinary microcrystals and renal epithelial cells is closely related to kidney stone formation. However, the mechanism of cell state changes that affect crystal–cell interaction remains unclear. Methods This study investigated the relationship between the sulfate group (–OSO 3 − ) content in Porphyra yezoensis polysaccharide (PYP) and the ability to repair damaged cells, as well as the changes in cell adhesion and endocytosis of nano-calcium oxalate monohydrate (COM) crystals before and after PYP repair of damaged renal tubular epithelial cells. The sulfur trioxide–pyridine method was used to sulfate PYP (–OSO 3 − content of 14.14%), and two kinds of sulfated PYPs with –OSO 3 − content of 20.28% (SPYP1) and 27.14% (SPYP2) were obtained. The above three PYPs were used to repair oxalate-damaged human proximal tubular epithelial cells (HK-2), and the changes in the biochemical indicators of the cells before and after the repair and the changes in cell adhesion and endocytosis of nano-COM crystals were detected. Results After repair by PYPs, the cell viability increased, the number of reactive oxygen species decreased, and the reduction of mitochondrial membrane potential and the release of intracellular Ca 2+ were suppressed. The cells repaired by PYPs inhibited the adhesion of nano-COM crystals while promoting the endocytosis of the adhered crystals. The endocytosed crystals mainly accumulated in the lysosome. The ability of PYPs to repair cell damage, inhibit crystal adhesion, and promote crystal endocytosis was enhanced when the –OSO 3 − content increased. Among them, SPYP2 with the highest –OSO 3 − content showed the best biological activity. Conclusion SPYP2 showed the best ability to repair damaged cells, followed by SPYP1 and PYP. SPYP2 may become a potential green drug that inhibits the formation and recurrence of calcium oxalate stones.

Dysregulated palmitic acid metabolism promotes the formation of renal calcium-oxalate stones through ferroptosis induced by polyunsaturated fatty acids/phosphatidic acid

“…Injury to renal tubular epithelial cells is considered to be an important cause of the formation of renal stones [ 39 ]. Changes in cell-membrane structure and adhesion sites for stone crystals happened in damaged cells [ 40 , 41 ].…”

Carboxymethylated Desmodium styracifolium polysaccharide reduces the risk of calcium oxalate kidney stone formation by inhibiting crystal adhesion and promoting crystal endocytosis

“…Endocytosis is an active transport process that consumes energy. Cells in good condition have high metabolism and sufficient energy and are more likely to endocytose crystals adhering to the cell surface and reduce the harm of adhering crystals to cells (Sun et al, 2021; Taguchi et al, 2021). Taguchi et al (Borjigin et al, 2023) demonstrated that a fatty acid–binding protein promoted the development of renal CaOx stones by attenuating the phagocytosis of crystals by macrophages and renal tubular cells.…”

“…I G U R E 13 Schematic diagram of carboxymethylated desmodium styracifolium polysaccharide inhibited the adhesion of nanoCOD crystals to HK-2 cell membranes and promoted crystal endocytosis. and are more likely to endocytose crystals adhering to the cell surface and reduce the harm of adhering crystals to cells(Sun et al, 2021;Taguchi et al, 2021).Taguchi et al (Borjigin et al, 2023) demonstrated that a fatty acid-binding protein promoted the development of renal CaOx stones by attenuating the phagocytosis of crystals by macrophages and renal tubular cells. Furthermore, CDSPs promoted nanoCOD crystal endocytosis(Figures 11 and 12), inhibited the nanoCOD crystal-induced opening of mPTPs in HK-2 cells (Figure6), increased the mitochondrial membrane potential (Figure5), and promoted the cell cycle transition from the G2/M and S phases to the G1 phase (Figure2).…”

Sulfated Undaria pinnatifida Polysaccharide Promotes Endocytosis of Nano-Calcium Oxalate Dihydrate by Repairing Subcellular Organelles in HK-2 Cells

“…Sulfated-modified polysaccharides are primarily used for antioxidant, antibacterial, antiviral, antitumor, anticoagulation, and immunomodulatory research [24][25][26]. However, less research has been conducted on their use in repairing damaged cells [27,28]. Previously, four sulfated U. pinnatifida polysaccharides (UPPs) were synthesized and their structures were characterized.…”