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ORIGINAL RESEARCH article

Front. Nutr.

Sec. Nutrition and Food Science Technology

Volume 12 - 2025 | doi: 10.3389/fnut.2025.1598991

This article is part of the Research TopicLipids in Foods and Nutrition: Innovative Analytical and Biochemical InsightsView all articles

α-Glycerol Monolaurate Promotes Tight Junction Proteins Expression through PKC/MAPK/ATF-2 Signaling Pathway

Provisionally accepted
Siyu  DaiSiyu Dai1Hong  WangHong Wang1*Dagang  LiDagang Li2*Cunjie  LiCunjie Li1
  • 1Guangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Jinan University, Guangzhou, China
  • 2Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

Introduction: This study investigates the effects of α-GML on intestinal epithelial tight junction (TJ) protein expression and its molecular mechanisms. Recognizing the critical role of TJ proteins in intestinal barrier function and the potential of α-GML to enhance this barrier, we employ the IPEC-J2 cell model. Our aim is to validate the regulatory impact ofα-GML on TJ protein expression and elucidate the underlying signaling pathways, thereby offering new strategies for intestinal health maintenance.Methods: Utilized Data-Independent Acquisition (DIA) analysis to identify optimal targets of α-GML in modulating Tight Junction (TJ) protein expression. Treated cells with specific inhibitors of PKC and MAPK to assess their role in TJ regulation by α-GML. Co-treated cells with the MAPK inhibitor SCH772984 and α-GML to study the effects on p-ATF-2 expression. Evaluated the effects of SCH772984 and ATF-2 overexpression on the protein expression levels of phosphorylated ATF-2, ZO-1, and OCLN.Results: Revealed that α-GML's modulation of TJ proteins might involve the PKC/MAPK signaling pathway, leading to ATF-2 phosphorylation. Both PKC and MAPK inhibitors reduced TJ protein expression(P<0.05, P<0.01 or P<0.001), indicating their involvement in α-GML's regulation.SCH772984 counteracted α-GML-induced upregulation of p-ATF-2 (P<0.05), suggesting MAPK's role in this process. Identified potential ATF-2 binding sites on ZO-1 and OCLN promoters. ATF-2 significantly enhanced ZO-1 promoter activity (P<0.001). SCH772984 reduced phosphorylated ATF-2, ZO-1, and OCLN levels(P<0.05 or P<0.01), while ATF-2 overexpression rescued this decrease(P<0.05 or P<0.01), confirming ATF-2's role in TJ protein upregulation via the MAPK pathway.Discussion: Our study indicated that α-GML enhanced the expression of TJ proteins through the PKC/MAPK/ATF-2 pathway, thereby enhancing the barrier function of intestinal epithelial cells.

Keywords: intestinal epithelial cells, Proteomic analysis, α- glycerol monolaurate, Tight Junction Proteins, PKC/MAPK/ATF-2 signaling pathway

Received: 24 Mar 2025; Accepted: 21 Jul 2025.

Copyright: © 2025 Dai, Wang, Li and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Hong Wang, Guangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Jinan University, Guangzhou, China
Dagang Li, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, Guangdong Province, China

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