Role of polymeric nanoparticle-mediated calcium influx in treating slow transit constipation based on ryanodine receptor 2 signaling pathway

Slow transit constipation (STC) has become a disease that seriously endangers public health. It is therefore essential to develop an effective strategy to prevent STC. Herein, this study explored the potential value of polymeric nanoparticles (NPs) on calcium (Ca 2+ ) influx release from sarcoplasmic reticulum and its role in STC. After preparation and characterization of NPs, STC intestinal epithelial cells were cultured and surface proteins were detected by flow cytometry, and then they were incubated with NPs. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect Ryanodine Receptor 2 (RyR2), protein kinase A (PKA) and Adenylate cyclase (AC) expression level, while the expressions of Ca 2+ leakage-specific proteins ORAI2 and Calreticulin (CRT) and related genes were also measured. Treatment with NPs resulted in a decreased expression of Ca 2+ leakage-specific genes, as well as reduced ORAI2, CRT, and Protein kinase A (KGF) levels, although their expressions were elevated over culture days. Of note is that, the expressions of PKA, RYR2 and AC increased in the presence of NPs, compared with control group. Collectively, the NPs hinder Ca 2+ influx, decrease expression of related genes and proteins, while activating RyR2 signaling pathways. These results suggest that, the NPs can restrict Ca 2+ influx, thereby improving STC through regulation of RyR2 signaling pathway.