Hyaluronic acid (HA) is a biopolymer composed of repeating units of disaccharides, which include molecules of D-glucuronic acid and N-acetylglucosamine molecules linked by β- (1 4) and β- (1 3)glycosides. It belongs to a group of substances called mucopolysaccharides belonging to the glycosaminoglycans (GAGs) family[1]. Hyaluronic acid also plays an important role in wound healing, ovulation, fertilization, signal transduction, and tumor physiology[2,3].
Hyaluronic acid oligosaccharides of a specific size range induce CD44 cleavage from tumor cells. It raise the possibility that small Hyaluronic acid oligosaccharides, which are known to occur in various tumor tissues, promote tumor invasion by enhancing the tumor cell motility that may be driven by CD44 cleavage[4]. Hyaluronic acid enhances tumor cell adhesion and migration and activates the Ras-mitogen-activated protein kinase pathway as well as the phosphoinositide 3-kinase pathway[5]. Purified autologous adipose-derived stem cells (ADSCs) combined with Hyaluronic acid facilitated adipose tissue regeneration in a rabbit subcutaneous model[7].
In mice, Cross-linked Hyaluronic acid had minimal effect on the early retention rate of surrounding fat grafts, but enhanced their vascularization. Fat grafts should be not injected into lumps of cross-linked HA. Therefore, agglomerated cross-linked Hyaluronic acid should be dissolved before fat transplantation[6]. Hyaluronic acid-NP treatment of diet-induced obese (DIO) mice reduced the epididymal fat mass and suppressed the induction of adipogenic and lipogenic regulators, while these effects were attenuated in the CD44-null mice[8]. In the animal study, the mice were fed a high-fat diet and treated with Clenbuterol by oral administration, or injected with Clenbuterol-modified Hyaluronic acid hydrogel (HAC) regularly. Both groups showed reduction in whole-body, visceral, and gonadal fat contents and body weight. The abdominal fat was analyzed using MRI imaging in adipose mode and water mode. The abdominal fat ratio in the mice treated with normal diet and those given intra-adipose injections with HAC had the lowest value among the test groups[9].
参考文献:
[1]. Salwowska NM, Bebenek KA, et,al.Physiochemical properties and application of hyaluronic acid: a systematic review. J Cosmet Dermatol. 2016 Dec;15(4):520-526. doi: 10.1111/jocd.12237. Epub 2016 Jun 21. PMID: 27324942.
[2]. HAMERMAN D, SCHUSTER H. Hyaluronate in normal human synovial fluid. J Clin Invest. 1958 Jan;37(1):57-64. doi: 10.1172/JCI103585. PMID: 13491713; PMCID: PMC293057.
[3]. Toole BP. Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer. 2004 Jul;4(7):528-39. doi: 10.1038/nrc1391. PMID: 15229478.
[4]. Sugahara KN, Murai T, et,al. Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells. J Biol Chem. 2003 Aug 22;278(34):32259-65. doi: 10.1074/jbc.M300347200. Epub 2003 Jun 11. PMID: 12801931.
[5]. Sohara Y, Ishiguro N, et,al. Hyaluronan activates cell motility of v-Src-transformed cells via Ras-mitogen-activated protein kinase and phosphoinositide 3-kinase-Akt in a tumor-specific manner. Mol Biol Cell. 2001 Jun;12(6):1859-68. doi: 10.1091/mbc.12.6.1859. PMID: 11408591; PMCID: PMC37347.
[6]. Zheng Z, Lei X, et,al.Changes in Human Fat Injected Alongside Hyaluronic Acid in the Backs of Nude Mice. Aesthet Surg J. 2021 May 18;41(6):NP631-NP642. doi: 10.1093/asj/sjaa351. PMID: 33326559.
[7]. Piccinno MS, Veronesi E, et,al. Adipose stromal/stem cells assist fat transplantation reducing necrosis and increasing graft performance. Apoptosis. 2013 Oct;18(10):1274-89. doi: 10.1007/s10495-013-0878-7. PMID: 23828239; PMCID: PMC3775159.
[8]. Lee WH, Rho JG, et,al.Self-assembled hyaluronic acid nanoparticle suppresses fat accumulation via CD44 in diet-induced obese mice. Carbohydr Polym. 2020 Jun 1;237:116161. doi: 10.1016/j.carbpol.2020.116161. Epub 2020 Mar 18. PMID: 32241446.
[9]. Chen WY, Lin FH. Oxidized Hyaluronic Acid Hydrogels as a Carrier for Constant-Release Clenbuterol Against High-Fat Diet-Induced Obesity in Mice. Front Endocrinol (Lausanne). 2021 Mar 12;12:572690. doi: 10.3389/fendo.2021.572690. PMID: 33776904; PMCID: PMC7996091.
透明质酸 (HA) 是由双糖的重复单元组成的生物聚合物，其中包括通过 β- (1 4) 和 β- (1 3) 糖苷连接的 D- 葡萄糖醛酸分子和 N- 乙酰氨基葡萄糖分子。它属于一组称为粘多糖的物质，属于糖胺聚糖 (GAG) 家族[1]。透明质酸还在伤口愈合、排卵、受精、信号转导和肿瘤生理学中发挥重要作用[2,3]。
特定大小范围的透明质酸寡糖诱导肿瘤细胞中的 CD44 裂解。它提出了一种可能性，即已知存在于各种肿瘤组织中的小透明质酸寡糖通过增强可能由 CD44 切割驱动的肿瘤细胞运动来促进肿瘤侵袭[4]。透明质酸可增强肿瘤细胞粘附和迁移，并激活 Ras-mitogen-activated protein kinase 通路以及磷酸肌醇 3-kinase 通路[5]。纯化的自体脂肪干细胞 (ADSCs) 结合透明质酸促进兔皮下模型的脂肪组织再生[7]。
在小鼠体内，交联透明质酸对周围脂肪移植物的早期保留率影响很小，但增强了它们的血管形成。不应将脂肪移植物注射到交联 HA 块中。因此，在脂肪移植前应溶解结块的交联透明质酸[6]。透明质酸-NP 治疗饮食诱导的肥胖 (DIO) 小鼠可减少附睾脂肪量并抑制脂肪生成和脂肪生成调节剂的诱导，而这些作用在 CD44 缺失小鼠中减弱 [8]。在动物研究中，小鼠被喂食高脂肪饮食，并通过口服克伦特罗治疗，或定期注射克仑特罗修饰的透明质酸水凝胶 (HAC)。两组均显示全身、内脏和性腺脂肪含量和体重都有所下降。使用脂肪模式和水模式下的 MRI 成像分析腹部脂肪。正常饮食组和脂肪内注射HAC组的小鼠腹脂率在各试验组中最低[9]。
| Cell experiment [1]: | |
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Cell lines |
The human pancreatic carcinoma cell line MIA PaCa-2 |
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Preparation Method |
MIA PaCa-2 cellsincubated with 10 μm MG132. The cells were then incubated with Hyaluronic acid for 1 h or with 100 ng/ml PMA for 30 min at 37 °C in the presence of 10 μm MG132, and the culture supernatants were collected for analysis by enzyme-linked immunosorbent assay (ELISA). |
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Reaction Conditions |
5-100ug/ml Hyaluronic acid for 1 h |
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Applications |
Hyaluronic acid oligosaccharides of a specific size range induce CD44 cleavage from tumor cells. |
| Animal experiment [2]: | |
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Animal models |
Male nude mice, 6 to 8 weeks old and weighing 22 to 28 g |
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Preparation Method |
The back of each mouse was divided into 4 regions that randomly received different treatments: no treatment, 0.30 mL Biohyalux ( Hyaluronic acid group), 0.30 mL fat (FAT group), and lumps formed by serial injection of 0.30 mL Biohyalux and 0.30 mL fat ( Hyaluronic acid /FAT group) |
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Dosage form |
0.30 mL Hyaluronic acid |
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Applications |
The expression levels of CD31 and vascular endothelial growth factor (VEGF) in the Hyaluronic acid/FAT group were higher than those in the FAT group, but the difference was only significant for VEGF expression. |
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参考文献: [1]. Sugahara KN, Murai T,et,al. Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells. J Biol Chem. 2003 Aug 22;278(34):32259-65. doi: 10.1074/jbc.M300347200. Epub 2003 Jun 11. PMID: 12801931. |
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