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FABP4 通过调节内质网应激和自噬来调节绵羊早期妊娠过程中子宫内膜上皮细胞的功能。

FABP4 mediates endoplasmic reticulum stress and autophagy to regulate endometrial epithelial cell function during early sheep gestation.

机构信息

College of Animal Science and Technology, Shihezi University, Xinjiang 832000, China.

Xinjiang Academy of Agriculture and Reclamation Sciences, Xinjiang 832000, China.

出版信息

J Reprod Dev. 2023 Dec 8;69(6):298-307. doi: 10.1262/jrd.2023-015. Epub 2023 Oct 2.

DOI:10.1262/jrd.2023-015
PMID:37779094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10721855/
Abstract

Dynamic changes in the endometrium are crucial for establishing early pregnancy in ruminants. Blastocyst elongation and implantation require hormones and nutrients to be secreted from the maternal endometrium. The fatty acid-binding protein FABP4 is a widely expressed fatty acid transport protein that promotes cell proliferation, migration, and invasion and is involved in conceptus implantation. However, the mechanism underlying the functional regulation of endometrial epithelial cells (EECs) by FABP4 during ovine peri-implantation remains unclear. We simulated hormonal changes in vitro in sheep EECs (SEECs) during the peri-implantation period and found that it elevated FABP4 expression. FABP4 inhibition significantly reduced cell migration, endoplasmic reticulum stress, and autophagy, suggesting that FABP4 regulates endometrial function in sheep. Moreover, the FABP4 inhibitor BMS309403 counteracted hormone-mediated functional changes in SEECs, and an endoplasmic reticulum stress activator and autophagy inhibitor reversed the abnormal secretion of prostaglandins induced by FABP4 inhibition. These results suggest that FABP4 affects ovine endometrial function during early gestation by regulating endoplasmic reticulum stress and autophagy in SEECs.

摘要

在反刍动物中，子宫内膜的动态变化对建立早期妊娠至关重要。囊胚的伸长和着床需要母体子宫内膜分泌的激素和营养物质。脂肪酸结合蛋白 FABP4 是一种广泛表达的脂肪酸转运蛋白，它促进细胞增殖、迁移和侵袭，并参与胚胎着床。然而，FABP4 在绵羊植入前期间对子宫内膜上皮细胞（EEC）的功能调节的机制尚不清楚。我们在体外模拟了绵羊 EEC（SEEC）在植入前期间的激素变化，发现它能上调 FABP4 的表达。FABP4 抑制显著减少细胞迁移、内质网应激和自噬，表明 FABP4 调节绵羊子宫内膜的功能。此外，FABP4 抑制剂 BMS309403 拮抗了激素介导的 SEEC 功能变化，内质网应激激活剂和自噬抑制剂逆转了 FABP4 抑制诱导的前列腺素异常分泌。这些结果表明，FABP4 通过调节 SEEC 中的内质网应激和自噬来影响绵羊早期妊娠的子宫内膜功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/c3893aae795d/jrd-69-298-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/7738cac3490d/jrd-69-298-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/1f8403607412/jrd-69-298-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/6b347fef923c/jrd-69-298-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/a10d272898c0/jrd-69-298-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/064920059491/jrd-69-298-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/c3893aae795d/jrd-69-298-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/7738cac3490d/jrd-69-298-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/1f8403607412/jrd-69-298-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/6b347fef923c/jrd-69-298-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/a10d272898c0/jrd-69-298-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/064920059491/jrd-69-298-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ed/10721855/c3893aae795d/jrd-69-298-g006.jpg

相似文献

[1]
FABP4 mediates endoplasmic reticulum stress and autophagy to regulate endometrial epithelial cell function during early sheep gestation.

J Reprod Dev. 2023-12-8

[2]
Hormone regulates endometrial function via cooperation of endoplasmic reticulum stress and mTOR-autophagy.

J Cell Physiol. 2018-4-10

[3]
Fatty Acid-Binding Protein 4 in Endometrial Epithelium Is Involved in Embryonic Implantation.

Cell Physiol Biochem. 2017

[4]
Expression and function of fatty acid-binding protein 4 in epithelial cell of uterine endometrium.

Cell Biol Int. 2015-5

[5]
COPS5 negatively regulates goat endometrial function via the ERN1 and mTOR-autophagy pathways during early pregnancy.

J Cell Physiol. 2019-3-29

[6]
FABP4 inhibitor BMS309403 protects against hypoxia-induced H9c2 cardiomyocyte apoptosis through attenuating endoplasmic reticulum stress.

J Cell Mol Med. 2020-10

[7]
Fatty Acid-Binding Protein 4 mediates apoptosis via endoplasmic reticulum stress in mesangial cells of diabetic nephropathy.

Mol Cell Endocrinol. 2015-8-15

[8]
FABP4 inhibitor BMS309403 decreases saturated-fatty-acid-induced endoplasmic reticulum stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation.

Biochim Biophys Acta Mol Cell Biol Lipids. 2018-3-15

[9]
infection-induced endoplasmic reticulum stress causes fatty acid-binding protein 4 secretion in murine adipocytes.

J Biol Chem. 2020-1-28

[10]
Knockdown of fatty acid binding protein 4 exacerbates Bacillus Calmette-Guerin infection-induced RAW264.7 cell apoptosis via the endoplasmic reticulum stress pathway.

Infect Genet Evol. 2020-11

引用本文的文献

[1]
ALKBH5 regulates intrauterine adhesion progression through m6A dependent FABP4 mRNA stabilization and serum lipid metabolism.

Commun Biol. 2025-7-1

[2]
FABP4 Mediates Inflammation to Regulate Endometrial Epithelial Cell Function During Early Gestation in Sheep.

Vet Med Sci. 2025-3

本文引用的文献

[1]
Single-cell transcriptomic characterization of sheep conceptus elongation and implantation.

Cell Rep. 2023-8-29

[2]
Epithelial-mesenchymal transition process during embryo implantation.

Cell Tissue Res. 2022-4

[3]
FABP4 promotes invasion and metastasis of colon cancer by regulating fatty acid transport.

Cancer Cell Int. 2020-10-19

[4]
FABP4 inhibitor BMS309403 protects against hypoxia-induced H9c2 cardiomyocyte apoptosis through attenuating endoplasmic reticulum stress.

J Cell Mol Med. 2020-10

[5]
Trop2 inhibition of P16 expression and the cell cycle promotes intracellular calcium release in OSCC.

Int J Biol Macromol. 2020-12-1

[6]
Anti-inflammatory Effect of Astragalin and Chlorogenic Acid on -Induced Inflammation of Sheep Endometrial Epithelium Cells.

Front Vet Sci. 2020-4-30

[7]
Adipocyte-Induced FABP4 Expression in Ovarian Cancer Cells Promotes Metastasis and Mediates Carboplatin Resistance.

Cancer Res. 2020-2-13

[8]
Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo.

Int J Mol Sci. 2020-1-30

[9]
Early Pregnancy Induces Expression of STAT1, OAS1 and CXCL10 in Ovine Spleen.

Animals (Basel). 2019-10-30

[10]
miR‑455 targets FABP4 to protect human endometrial stromal cells from cytotoxicity induced by hydrogen peroxide.

Mol Med Rep. 2019-10-4

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