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视黄酸接枝透明质酸激活维甲酸基因表达并从细胞膜中去除胆固醇。

Retinoic Acid Grafted to Hyaluronic Acid Activates Retinoid Gene Expression and Removes Cholesterol from Cellular Membranes.

机构信息

R&D Department, Contipro, a.s., 562 04 Dolní Dobrouč, Czech Republic.

Third Faculty of Medicine, Charles University, 100 00 Prague, Czech Republic.

出版信息

Biomolecules. 2022 Jan 25;12(2):200. doi: 10.3390/biom12020200.

DOI:10.3390/biom12020200
PMID:35204701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8961547/
Abstract

All-trans-retinoic acid (atRA) is a potent ligand that regulates gene expression and is used to treat several skin disorders. Hyaluronic acid (HA) was previously conjugated with atRA (HA-atRA) to obtain a novel amphiphilic compound. HA-atRA forms micelles that incorporate hydrophobic molecules and facilitate their transport through the skin. The aim of this study was to determine the influence of HA-atRA on gene expression in skin cells and to compare it with that of unbound atRA. Gene expression was investigated using microarrays and a luciferase system with a canonical atRA promoter. HA-atRA upregulated gene expression similarly to atRA. However, HA-atRA activated the expression of cholesterol metabolism genes, unlike atRA. Further investigation using HPLC and filipin III staining suggested that the treated cells induced cholesterol synthesis to replenish the cholesterol removed from the cells by HA-atRA. HA modified with oleate (HA-C18:1) removed cholesterol from the cells similarly to HA-atRA, suggesting that the cholesterol removal stemmed from the amphiphilic nature of the two derivatives. HA-atRA induces retinoid signaling. Thus, HA-atRA could be used to treat skin diseases, such as acne and psoriasis, where the combined action of atRA signaling and anti-inflammatory cholesterol removal may be potentially beneficial.

摘要

全反式视黄酸（atRA）是一种有效的配体，可调节基因表达，用于治疗多种皮肤疾病。 透明质酸（HA）以前与 atRA 结合（HA-atRA）以获得新型两亲性化合物。HA-atRA 形成胶束，可容纳疏水分子并促进其通过皮肤运输。本研究旨在确定 HA-atRA 对皮肤细胞中基因表达的影响，并将其与未结合的 atRA 进行比较。使用微阵列和带有经典 atRA 启动子的荧光素酶系统研究基因表达。HA-atRA 对基因表达的上调作用与 atRA 相似。但是，HA-atRA 激活了胆固醇代谢基因的表达，而 atRA 则没有。使用 HPLC 和 filipin III 染色的进一步研究表明，处理后的细胞诱导胆固醇合成以补充由 HA-atRA 从细胞中去除的胆固醇。与 HA-atRA 类似，用油酸修饰的 HA（HA-C18:1）从细胞中去除胆固醇，表明胆固醇的去除源于两种衍生物的两亲性质。HA-atRA 诱导视黄酸信号。因此，HA-atRA 可用于治疗痤疮和银屑病等皮肤疾病，atRA 信号和抗炎性胆固醇去除的联合作用可能是有益的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/707e10cfbf96/biomolecules-12-00200-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/2d34a69afb18/biomolecules-12-00200-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/e3912b3a5301/biomolecules-12-00200-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/c56cf21d8c2d/biomolecules-12-00200-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/54743c1f2587/biomolecules-12-00200-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/f15602bbc1a5/biomolecules-12-00200-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/707e10cfbf96/biomolecules-12-00200-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/2d34a69afb18/biomolecules-12-00200-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/e3912b3a5301/biomolecules-12-00200-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/c56cf21d8c2d/biomolecules-12-00200-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/54743c1f2587/biomolecules-12-00200-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/f15602bbc1a5/biomolecules-12-00200-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e7/8961547/707e10cfbf96/biomolecules-12-00200-g006.jpg

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