Role of the GalNAc-galectin pathway in the healing of premature rupture of membranes.

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Medicine Pub Date : 2024-09-04 DOI:10.1186/s10020-024-00908-6

Jia-Le Chen, Lou Liu, Xin-Rui Peng, Yan Wang, Xiang Xiang, Yu Chen, De-Xiang Xu, Dao-Zhen Chen

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引用次数: 0

Abstract

Background: Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing.

Methods: An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing.

Results: GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P < 0.05). GalNAc promoted the expression of Gal-1 and Gal-3 with anti-inflammatory and anti-oxidative stress effects. GalNAc promoted the migration of hAECs (50% vs. 80%) and WISH cells through the Akt signaling pathway, EMT reached the point of promoting fetal membrane healing, and GalNAc did not affect the activity of hAECs and WISH cells (P > 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P < 0.05) but did not affect HA levels (P > 0.05).

Conclusions: GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.

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GalNAc-Galectin 通路在胎膜早破愈合中的作用。

背景：胎膜早破（PROM）是早产的一个主要原因，也是新生儿死亡和发病的一个主要原因。天然产物 N-乙酰-d-半乳糖胺（GalNAc）是生物细胞或组织中重要多糖（如甲壳素、糖蛋白和糖脂）的基本组成成分，可改善伤口愈合的可能效果：方法：利用肿瘤坏死-α（TNF-α）和脂多糖（LPS）对 WISH 细胞的作用，构建了一个体外炎症和氧化应激模型。人羊膜上皮细胞（hAECs）主要通过消化培养来构建伤口模型。采用DCFH-DA荧光探针、ELISA、CCK-8、划痕、透孔迁移和Western blot等方法分析了GalNAc对hAECs和WISH细胞抗炎和抗氧化应激、迁移和增殖、上皮-间质转化（EMT）、糖胺聚糖（GAG）/透明质酸（HA）生成和蛋白激酶B（Akt）通路的影响，以确定GalNAc促进羊膜伤口愈合的机制。结果GalNAc 降低了 TNF-α 刺激的 WISH 细胞中 IL-6 的表达和 LPS 刺激的 WISH 细胞中 ROS 的表达（P 0.05）。GalNAc 上调了 WISH 细胞中 sGAG 的表达（P 0.05）：GalNAc可能是通过galectin通路预防和治疗PROM的潜在靶点，包括(i)炎症；(ii)上皮-间质转化；(iii)增殖和迁移；以及(iv)回归、重塑和愈合。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.