(P04-069-24) The Inhibitory Effects of Trigonelline-Induced Altered Secreted Proteins From Renal Tubular Cells on Calcium Oxalate Crystals: Implications for Kidney Stone Prevention

Objectives: Trigonelline is an important bioactive compound found in several edible plants and has therapeutic potential in various human diseases. Although recent studies have suggested its potential to prevent kidney stone disease, mechanisms underlying its anti-lithiatic effects remained unclear and were therefore addressed in this study.

Methods: The secretome (an extracellular compartment containing a large number of secreted proteins) was collected and purified from (100 µM) trigonelline-treated MDCK renal tubular cells (namely “trigonelline-treated secretome”) to evaluate its effects on calcium oxalate (CaOx) crystals compared with that derived from untreated cells (namely “control secretome”). Quantitative proteomics using nanoLC-ESI-Qq-TOF MS/MS was employed to compare the trigonelline-treated secretome with the control secretome. Bioinformatic analyses were then performed to obtain additional information and physicochemical properties of the differentially secreted proteins.

Results: Trigonelline-treated secretome significantly decreased CaOx crystal size, number and abundance during initial crystallization, and also reduced crystal growth, aggregation and adhesion to renal cells. Quantitative proteomics identified 46 differentially secreted (35 increased and 11 decreased) proteins in the trigonelline-treated secretome. While most of the identified proteins were acidic, the significantly increased secreted proteins had an increased proportion of basic proteins, resulting in a slightly greater isoelectric point. In concordance, the significantly increased secreted proteins had a greater proportion of positively charged amino acids as compared with the significantly decreased secreted proteins. However, proportions of aromatic, polar, non-polar, and negatively charged amino acids were comparable.

Conclusions: We report herein the direct evidence of the inhibitory effects of trigonelline against CaOx crystallization, growth, aggregation and adhesion to renal cells via the induction of altered secreted proteins that show some unique physicochemical properties when the increased secreted proteins were compared with the decreased compartments. These data may lead to a better understanding of the mechanisms underlying the anti-lithiatic effects of trigonelline to prevent kidney stone disease.

Funding Sources: N/A