Heparan sulfate (HS) is a complex, polyanionic polysaccharide ubiquitously expressed on cell surfaces and in the extracellular matrix[1]. Heparan sulfate interacts with numerous proteins, including growth factors, morphogens, and adhesion molecules, and thereby regulates important developmental processes in invertebrates and vertebrates[6]. Heparan sulfate proteoglycans can act as receptors for proteases and protease inhibitors regulating their spatial distribution and activity. Membrane Heparan sulfate proteoglycans act as coreceptors for various tyrosine kinase-type growth factor receptors, lowering their activation threshold or changing the duration of signaling reactions[5].
Heparan sulfate treatment significantly reduced SARS-CoV-2 replication in cell lysates and supernatant samples of Calu3 and Caco2. HS serves as an essential host determinant during SARS-CoV-2 attachment and replication[2].Heparan sulfate influences the binding affinity of intestinal epithelium cells to Wnt, thereby promoting activation of canonical Wnt signaling and facilitating regeneration of small intestinal crypts after epithelial injury[7].
In Sprague-Dawley male rats, FGF-2/FGFR system is involved in the regulation of astrocytic reactivity and/or proliferation in the brain and its action is potentiated by Heparan sulfate [3].Heparan sulfate proteoglycans represent a major component of the extracellular matrix and are critical for brain development, Heparan Sulfate can maintain neuronal excitability, promote synaptic plasticity and learning[5].
参考文献:
[1]: Chhabra M, Doherty GG, et,al. From Cancer to COVID-19: A Perspective on Targeting Heparan Sulfate-Protein Interactions. Chem Rec. 2021 Nov;21(11):3087-3101. doi: 10.1002/tcr.202100125. Epub 2021 Jun 19. PMID: 34145723; PMCID: PMC8441866.
[2]: Chu H, Hu B, et,al. Host and viral determinants for efficient SARS-CoV-2 infection of the human lung. Nat Commun. 2021 Jan 8;12(1):134. doi: 10.1038/s41467-020-20457-w. PMID: 33420022; PMCID: PMC7794309.
[3]: Gómez-Pinilla F, Vu L, et,al. Regulation of astrocyte proliferation by FGF-2 and heparan sulfate in vivo. J Neurosci. 1995 Mar;15(3 Pt 1):2021-9. doi: 10.1523/JNEUROSCI.15-03-02021.1995. PMID: 7891149; PMCID: PMC6578134.
[4]: Minge D, Senkov O, et,al. Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination. Cereb Cortex. 2017 Feb 1;27(2):903-918. doi: 10.1093/cercor/bhx003. PMID: 28119345; PMCID: PMC5390399.
[5]: Sarrazin S, Lamanna WC, et,al. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol. 2011 Jul 1;3(7):a004952. doi: 10.1101/cshperspect.a004952. PMID: 21690215; PMCID: PMC3119907.
[6]: Kraushaar DC, Dalton S, et,al. Heparan sulfate: a key regulator of embryonic stem cell fate. Biol Chem. 2013 Jun;394(6):741-51. doi: 10.1515/hsz-2012-0353. PMID: 23370908; PMCID: PMC3933957.
[7]: Yamamoto S, Nakase H, et,al. Heparan sulfate on intestinal epithelial cells plays a critical role in intestinal crypt homeostasis via Wnt/β-catenin signaling. Am J Physiol Gastrointest Liver Physiol. 2013 Aug 1;305(3):G241-9. doi: 10.1152/ajpgi.00480.2012. Epub 2013 Jun 6. PMID: 23744737; PMCID: PMC3742857.
硫酸乙酰肝素 (HS) 是一种复杂的聚阴离子多糖，广泛表达于细胞表面和细胞外基质[1]。硫酸乙酰肝素与许多蛋白质相互作用，包括生长因子、形态发生素和粘附分子，从而调节无脊椎动物和脊椎动物的重要发育过程[6]。硫酸乙酰肝素蛋白聚糖可以作为蛋白酶和蛋白酶抑制剂的受体，调节它们的空间分布和活性。膜硫酸乙酰肝素蛋白多糖作为多种酪氨酸激酶型生长因子受体的辅助受体，降低其激活阈值或改变信号反应的持续时间[5]。
硫酸乙酰肝素处理显着降低了 Calu3 和 Caco2 细胞裂解物和上清液样品中的 SARS-CoV-2 复制。 HS 在 SARS-CoV-2 附着和复制过程中作为重要的宿主决定因素[2]。硫酸乙酰肝素影响肠上皮细胞与 Wnt 的结合亲和力，从而促进经典 Wnt 信号通路的激活并促进再生上皮损伤后小肠隐窝的形成[7].
在 Sprague-Dawley 雄性大鼠中，FGF-2/FGFR 系统参与脑内星形胶质细胞反应性和/或增殖的调节，硫酸乙酰肝素可增强其作用[3]。硫酸乙酰肝素蛋白多糖是细胞外基质的主要成分，对大脑发育至关重要，硫酸乙酰肝素可维持神经元兴奋性，促进突触可塑性和学习[5]。
| Cell experiment [1]: | |
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Cell lines |
Calu3 (lung epithelium) and Caco2 (intestinal epithelium) cells |
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Preparation Method |
Calu3 (lung epithelium) and Caco2 (intestinal epithelium) cells were infected with early passage SARS-CoV-2 pretreated with Heparan sulfate, and samples were collected 24 hours after infection. |
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Reaction Conditions |
0-500ug/ml Heparan sulfate,24h |
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Applications |
Heparan sulfate treatment significantly reduced SARS-CoV-2 replication in cell lysates and supernatant samples of Calu3 and Caco2. |
| Animal experiment [2]: | |
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Animal models |
Sprague-Dawley male rats 3-4 months old |
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Preparation Method |
Groups of rats (n = 5) received a piece of Gelfoam embedded with human recombinant FGF-2 dissolved in PBS, Heparan sulfate (HS; 10 μg/ml) dissolved in PBS, or both, in the right hemispheres. |
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Dosage form |
A piece of Gelfoam embedded with 10 ug/ml Heparan sulfate for two days |
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Applications |
FGF-2/FGFR system is involved in the regulation of astrocytic reactivity and/or proliferation in the brain and its action is potentiated by Heparan sulfate. |
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参考文献: [1]. Chu H, Hu B, et,al. Host and viral determinants for efficient SARS-CoV-2 infection of the human lung. Nat Commun. 2021 Jan 8;12(1):134. doi: 10.1038/s41467-020-20457-w. PMID: 33420022; PMCID: PMC7794309. [2]. Gómez-Pinilla F, Vu L, et,al. Regulation of astrocyte proliferation by FGF-2 and heparan sulfate in vivo. J Neurosci. 1995 Mar;15(3 Pt 1):2021-9. doi: 10.1523/JNEUROSCI.15-03-02021.1995. PMID: 7891149; PMCID: PMC6578134. |
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