PepT1 Expression Helps Maintain Intestinal Homeostasis by Mediating the Differential Expression of miRNAs along the Crypt-Villus Axis

Yuchen Zhang,Mingzhen Zhang,Lewins Walter,Didier Merlin,Pallavi Garg,Emilie Viennois,Moon Kwon Han,Bo Xiao

doi:10.1038/srep27119

Yuchen Zhang, Mingzhen Zhang + Show 6 more

Open Access

https://doi.org/10.1038/srep27119

Copy DOI

Abstract

In the jejunum, PepT1 is particularly enriched in the well-differentiated absorptive epithelial cells in the villi. Studies of expression and function of PepT1 along the crypt-villus axis demonstrated that this protein is crucial to the process of di/tripeptide absorption. We recently exhibited that PepT1 plays an important role in multiple biological functions, including the ability to regulate the expression/secretion of specific microRNAs (miRNAs) and the expression levels of multiple proteins. In this study, we observed that PepT1 knockout (KO) mice exhibited reduced body weight and shorten intestinal microvilli. We then examined the expression levels of various miRNAs and their target proteins along the crypt-villi axis in the jejunum of PepT1 KO mice. We found that PepT1 KO altered the distribution of miRNAs along the crypt-villus axis and changed the miRNA profiles of both villi and crypts. Using miRNA-target prediction and 2D-DIGE/mass spectrometry on villi and crypts samples, we found that ablation of PepT1 further directly or indirectly altered expression levels of certain protein targets. Collectively, our results suggest that PepT1 contributes to maintain balance of homeostasis and proper functions in the small intestine, and dysregulated miRNAs and proteins along the crypt-villus axis are highly related to this process.

Highlights

It has been reported that PepT1 is mostly expressed in the small intestine, but in limited level or absent in the colon, kidney, pancreas and bile duct[16,17,18,19,20]
Our results support the emerging idea that PepT1 plays an important role in multiple biological processes, as we show for the first time that it critically regulates directly or indirectly the miRNA and protein expression along the crypt/villus axis in the jejunum, and helps maintain intestinal homeostasis
The size of microvilli at the apical membranes of enterocytes was much lower in PepT1 KO than in WT animals (1.14 ± 0.14 vs. 1.29 ± 0.07 mm; n = 27) (Fig. 1f,g), suggesting that knockout of PepT1 in the small intestine resulted in defective microvilli at the brush borders of apical surfaces of mouse villus enterocytes

Summary

Introduction

It has been reported that PepT1 is mostly expressed in the small intestine, but in limited level or absent in the colon, kidney, pancreas and bile duct[16,17,18,19,20]. The expression/function of PepT1 along the crypt-villus axis suggests that the protein is specific to the well differentiated absorptive epithelial cells, strengthening the notion that PepT1 is important to the absorption process[17,26]. To get a better understanding of PepT1 functions and their influence on the small intestinal homeostasis, we first investigated miRNA expression patterns along the crypt/villus axis in the jejunum of wild-type (WT) mice, where PepT1 is highly expressed. Our results support the emerging idea that PepT1 plays an important role in multiple biological processes, as we show for the first time that it critically regulates directly or indirectly the miRNA and protein expression along the crypt/villus axis in the jejunum, and helps maintain intestinal homeostasis

Methods

Results

Conclusion