2. Academic Validation
  3. L-glutamate requires β-catenin signalling through Frizzled7 to stimulate porcine intestinal stem cell expansion

L-glutamate requires β-catenin signalling through Frizzled7 to stimulate porcine intestinal stem cell expansion

  • Cell Mol Life Sci. 2022 Sep 19;79(10):523. doi: 10.1007/s00018-022-04545-2.
Ying-Chao Qin  # 1,  Jia-Yi Zhou  # 1,  Min Zhu 2,  Geng-Xiu Zan 1,  Chun-Qi Gao 1,  Hui-Chao Yan 1,  Xiang-Guang Li 3,  Xiu-Qi Wang 4
Affiliations

Affiliations

  • 1 College of Animal Science, South China Agricultural University/Guangdong Laboratory for Lingnan Modern Agriculture/Guangdong Provincial Key Laboratory of Animal Nutrition Control/National Engineering Research Center for Breeding Swine Industry, Guangzhou, 510642, China.
  • 2 College of Animal Science, Guizhou University, Guiyang, 550025, China.
  • 3 Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. xgli@gdut.edu.cn.
  • 4 College of Animal Science, South China Agricultural University/Guangdong Laboratory for Lingnan Modern Agriculture/Guangdong Provincial Key Laboratory of Animal Nutrition Control/National Engineering Research Center for Breeding Swine Industry, Guangzhou, 510642, China. xqwang@scau.edu.cn.
  • # Contributed equally.
PMID: 36121491 DOI: 10.1007/s00018-022-04545-2
Abstract

Intestinal stem cells (ISCs) decode and coordinate various types of nutritional information from the diet to support the crypt-villus axis architecture, but how specific dietary molecules affect intestinal epithelial homeostasis remains unclear. In the current study, L-glutamate (Glu) supplementation in either a nitrogen-free diet (NFD) or a corn-soybean meal diet (CSMD) stimulated gut growth and ISC expansion in weaned piglets. Quantitative proteomics screening identified the canonical Wnt signalling pathway as a central regulator of intestinal epithelial development and ISC activity in vivo. Importantly, the Wnt transmembrane receptor Frizzled7 (FZD7) was upregulated in response to dietary Glu patterns, and its perturbations in intestinal organoids (IOs) treated with a specific inhibitor and in FZD7-KO IPEC-J2 cells disrupted the link between Glu inputs and β-catenin signalling and a subsequent reduction in cell viability. Furthermore, co-localization, coimmunoprecipitation (Co-IP), isothermal titration calorimetry (ITC), and microscale thermophoresis (MST) revealed that Glu served as a signalling molecule directly bound to FZD7. We propose that FZD7-mediated integration of the extracellular Glu signal controls ISC proliferation and differentiation, which provides new insights into the crosstalk of nutrients and ISCs.

Keywords

Frizzled7; Glutamate; Intestinal stem cells; Piglets; β-Catenin.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P1454A
    99.35%, FZD7受体拮抗剂
    Wnt
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z