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 (Ca2+) influx release from sarcoplasmic reticulum and its role in IP: 203 8 10 .20 On Tue 08 Aug 2023 05:08:35 STC. After preparation and characterization of NPs, STC intestinal epitlial cells were cultured and surface Copyright American Sc entific Publishers proteins were detected by flow cytometry, and then they were icubated with NPs. Enzyme-linked immunosorDelivered by Ingenta bent assay (ELISA) was conducted to detect Ryanodine Receptor 2 (RyR2), protein kinase A (PKA) and Adenylate cyclase (AC) expression level, while the expressions of Ca2+ leakage-specific proteins ORAI2 and Calreticulin (CRT) and related genes were also measured. Treatment with NPs resulted in a decreased expression of Ca2+ 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 Ca2+ influx, decrease expression of related genes and proteins, while activating RyR2 signaling pathways. These results suggest that, the NPs can restrict Ca2+ influx, thereby improving STC through regulation of RyR2 signaling pathway.