Autophagy Regulates Putative Anion Transporter 1 Expression in Intestinal Epithelial Cells

Putative anion transporter 1 (PAT-1) is the key oxalate-secreting transporter in the intestine and therefore, maintaining its steady-state levels is critical for oxalate homeostasis. Autophagy is known to modulate the expression of intestinal solute transporters; however, its role in regulating PAT-1 has not been examined. Autophagy in Caco-2 cells was induced by either rapamycin treatment or by nutrient deprivation and assessed by conventional autophagy marker proteins. ATG7 (autophagy-related 7) protein expression was attenuated by ATG7-siRNA in Caco-2 cells or by utilising ATG7KO mice. PAT-1 protein levels in Caco-2 cells were significantly reduced by rapamycin or by nutrient deprivation at 48 and 72 h. Concomitantly, the LC3II/I ratio was increased, and p62 levels were significantly decreased, confirming the induction of autophagy. Nutrient deprivation for 6 h also caused a significant decrease in the surface levels of PAT-1. PAT-1 protein levels were increased by the siRNA-mediated ATG7 knockdown in Caco-2 cells and in the ileum of ATG7KO mice. In summary, Autophagy in intestinal epithelial cells modulates the basal levels of PAT-1 protein and may play a critical role in the maintenance of oxalate homeostasis.