Mammalian Target of Rapamycin Signaling Pathway Changes with Intestinal Epithelial Cells Renewal Along Crypt-Villus Axis

Abstract

Background/Aims: Understanding the mechanism that involves in regulating epithelial cells renewal is the fundamental of regulating intestinal mucosa development and functions and related diseases. The mechanistic target of rapamycin (mTOR) signaling pathway involves in controlling various major processes by integrating intracellular and extracellular cues. The present experiment was conducted to test the correlation between the mTOR signaling pathway and intestinal epithelial cells renewal along crypt-villus axis (CVA). Methods: Intestinal epithelial cells were sequentially isolated from the jejunum of piglets along CVA, and the amount or phosphorylation level of proteins involved in cell cycle, mTOR signaling pathway, gene expression, and the antioxidant capacity in the isolated cells were measured. Results: The results showed that the amount of proteins involved in cell cycle decreased from crypt to villus tip. The amount or phosphorylation level of proteins related to mTOR signaling pathway in intestinal epithelial cells mainly decreased during maturation along CVA. The amount of proteins involved in gene expression and the antioxidant capacity also decreased from crypt to the top of villi. Conclusions: These results indicate that the mTOR signaling pathway may be involved in regulating the intestinal epithelial cells renewal along CVA and it may partly through affecting the antioxidant capacity and gene expression of intestinal epithelial cells. Further histological verification is needed to confirm the results of the present experiments.

Dietary sulfur amino acids affect jejunal cell proliferation and functions by affecting antioxidant capacity, Wnt/β-catenin, and the mechanistic target of rapamycin signaling pathways in weaning piglets1

“…This ensures intestinal function and recovery from tissue damage (Fan et al, 2001;Yang et al, 2013a;Yang et al, 2016a). Intestinal epithelial cell renewal along the CVA is regulated by mechanistic targeting of rapamycin (mTOR), Wnt/β-catenin signaling pathways, and antioxidant capacity (Yang et al, 2013(Yang et al, , 2016b. Weaning stress in piglets usually disrupts intestinal epithelial cell renewal along the CVA and related signaling pathways and can result in morphological intestinal atrophy and dysfunction (Jiang et al, 2000;Yang et al, 2013a).…”

First Degree Relatives of Patients with Celiac Disease Harbour an Intestinal Transcriptomic Signature that Might Protect them from Enterocyte Damage

“…At the molecular level the mTOR (mechanistic target of rapamycin) pathway, which has been shown to be central to the maintenance of the crypt-villous axis, is regulated in FDR in a way that promotes the formation of villi. The mTOR C1 and c myc - APC pathways have been shown to be essential in regulation of the crypt-villous architecture 18 , 19 . These studies also show that the mTOR C1 pathway is progressively downregulated from the crypt to the villous and that this may be involved in regulating epithelial cell renewal along the crypt-villous axis.…”

Nutritional intervention for the intestinal development and health of weaned pigs

“…Several recently published research articles revealed the impacts of weaning stress on the expression of proteins and metabolites in enterocytes of piglets (15)(16)(17)(18)(19)(20). Weaning significantly down-regulated the expression of proteins involved in the tricarboxylic acid cycle, β-oxidation, and the glycolysis pathway in the upper villus and middle villus of the jejunum in early-weaned pigs, but up-regulated proteins involved in glycolysis in crypt cells (15).…”