title: PepT1 Expression Helps Maintain Intestinal Homeostasis by Mediating the Differential Expression of miRNAs along the Crypt-Villus Axis.
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.
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, 30302, USA.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, 30302, USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Viennois
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, 30302, USA.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, 30302, USA.|Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, 30302, USA.
authors.forename: Moon Kwon
authors.initials: MK
authors.lastname: Han
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, 30302, USA.
authors.forename: Lewins
authors.initials: L
authors.lastname: Walter
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia, 30302, USA.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Garg
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, 30302, USA.|Atlanta Veterans Affairs Medical Center, Decatur, Georgia, 30033, USA.
authors.forename: Didier
authors.initials: D
authors.lastname: Merlin
mesh_terms: D000818:Animals; D049628:Body Size; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D053263:Gene Regulatory Networks; D006706:Homeostasis; D007421:Intestine, Small / Q000002:abnormalities* / Q000502:physiology; D007583:Jejunum / Q000002:abnormalities / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D000074011:Peptide Transporter 1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D000074011:Peptide Transporter 1; C489941:Slc15a1 protein, mouse