研究报告

透明质酸干预成纤维细胞分泌改善角质形成细胞缺氧损伤

  • 刘静 ,
  • 朴美善 ,
  • 蓝兴眉 ,
  • 杨成 ,
  • 赵炳天
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  • 1(江南大学 化学与材料工程学院,江苏 无锡,214000)
    2(无锡市第二人民医院,江苏 无锡,214000)
第一作者:博士研究生(杨成教授和赵炳天副研究员为共同通信作者,E-mail:cyang@jiangnan.edu.cn;btzhao@jiangnan.edu.cn)

收稿日期: 2025-11-28

  修回日期: 2025-12-19

  网络出版日期: 2026-06-15

基金资助

无锡市卫生健康委科研项目(M202452)

Hyaluronic acid attenuates keratinocyte hypoxia by modulating fibroblast secretion

  • LIU Jing ,
  • PIAO Meishan ,
  • LAN Xingmei ,
  • YANG Cheng ,
  • ZHAO Bingtian
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  • 1(School of Chemical and Materials Engineering, Jiangnan University, Wuxi 214000, China)
    2(The Affiliated Wuxi No.2 People’s Hospital, Wuxi 214000, China)

Received date: 2025-11-28

  Revised date: 2025-12-19

  Online published: 2026-06-15

摘要

透明质酸(hyaluronic acid, HA)凭借其良好的生物活性与成熟的发酵工艺,已成为食品、化妆品及医药等多个领域中广泛应用的原料之一。尽管HA被证实对皮肤健康具有显著的促进作用,但其通过细胞间相互作用抵御皮肤缺氧损伤的作用机制尚不明确。该研究采用4种不同分子质量HA预处理成纤维细胞制备条件培养基(HA-conditioned medium, HA-CM),并进一步评估HA-CM对角质形成细胞缺氧损伤的改善作用。结果表明,低分子质量HA2(30.8 kDa)在促进成纤维细胞分泌转化生长因子-β1(transforming growth factor-beta 1, TGF-β1)与血管内皮生长因子(vascular endothelial growth factor, VEGF),以及抑制白细胞介素-1α(interleukin-1 alpha, IL-1α)释放方面,显示出最强的效应。此外,HA2-CM对缺氧损伤HaCaT细胞的保护作用最为显著,表现为活性氧(reactive oxygen species, ROS)水平降低,肿瘤坏死因子-α(tumor necrosis factor-alpha, TNF-α)和白细胞介素-6(interleukin-6, IL-6)分泌减少以及细胞凋亡率下降。上述结果表明HA通过重塑成纤维细胞的分泌表型,以TGF-β1/VEGF为关键旁分泌媒介,协同激活核因子E2相关因子2(nuclear factor erythroid 2-related factor 2, Nrf2)/血红素加氧酶-1(heme oxygenase-1, HO-1)通路的抗氧化作用,从而阐释了其对皮肤缺氧损伤进行多靶点调控的机制。该文为综合利用透明质酸开发高附加值的食品指明了方向,也为基于分子质量精准设计的抗缺氧干预策略提供了重要参考。

本文引用格式

刘静 , 朴美善 , 蓝兴眉 , 杨成 , 赵炳天 . 透明质酸干预成纤维细胞分泌改善角质形成细胞缺氧损伤[J]. 食品与发酵工业, 2026 , 52(10) : 308 -315 . DOI: 10.13995/j.cnki.11-1802/ts.045329

Abstract

Hyaluronic acid (HA) is a widely used ingredient in foods, cosmetics, and pharmaceuticals due to its favorable biological activities and well-established microbial fermentation processes.Although HA has been shown to significantly promote skin health, its mechanism of action in alleviating skin hypoxic injury through intercellular crosstalk remains unclear.In this study, fibroblasts were pretreated with HA of four distinct molecular weights to generate HA-conditioned medium (HA-CM), and the protective effects of the HA-CM against hypoxic injury in keratinocytes were subsequently evaluated.The results showed that low-molecular-weight HA (HA2, 30.8 kDa) exhibited the strongest effect in promoting fibroblast secretion of transforming growth factor-beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF), while simultaneously suppressing the release of interleukin-1 alpha (IL-1α).Moreover, HA2-CM conferred the most pronounced protection against hypoxic damage in HaCaT cells, as evidenced by reduced reactive oxygen species (ROS) accumulation, decreased secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and lower apoptosis rate.These findings demonstrate that HA reprograms the fibroblast secretory phenotype, using TGF-β1 and VEGF as key paracrine mediators to synergistically activate the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathway, thereby establishing a multi-target regulatory mechanism against skin hypoxic injury.This work provides direction for the comprehensive utilization of HA in developing high-value-added functional foods and offers an important reference for the molecular-weight-tailored design of anti-hypoxia interventions.

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