无机纳米材料作为细胞肝纤维化的高效抑制剂,ACS Applied Materials & Interfaces

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无机纳米材料作为细胞肝纤维化的高效抑制剂
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2018-08-29 00:00:00 , DOI: 10.1021/acsami.8b10527
Fei Peng ₁ , Jie Kai Tee _{1,

2} , Magdiel Inggrid Setyawati ₃ , Xianguang Ding ₃ , Hui Ling Angie Yeo ₁ , Yeong Lan Tan _{1,

2} , David Tai Leong ₃ , Han Kiat Ho ₁

Affiliation

慢性肝功能不全通常始于肝纤维化。迄今为止，尚未批准有效的抗纤维化药物用于人类临床。在当前的工作中，二氧化钛（TiO ₂）纳米颗粒（NPs）和二氧化硅（SiO ₂NP被用作具有内在化学-物理性质的活性抑制剂，通过作用于肝星状细胞（HSC，用于沉积在纤维化中见到的瘢痕组织的肝脏机制）来阻断纤维化和相关的表型。使用LX-2细胞作为HSC模型，发现内在化的纳米材料可抑制细胞纤维化的经典结局，例如抑制胶原I（Col-I）和α平滑肌肌动蛋白（α-SMA）的表达，这是通过转化产生的生长因子β（TGF-β）激活的HSCs呈浓度依赖性和时间依赖性。在生物化学上，这些纳米材料还可以通过上调基质金属蛋白酶（MMPs）和下调MMPs组织抑制剂（TIMPs）来促进胶原蛋白的降解。此外，通过调节上皮-间质转化（EMT）基因[例如E-钙粘蛋白（E-Cad）和N-钙粘蛋白（N-Cad）]，纳米材料处理的TGF-β激活的LX-2细胞的粘附和迁移特性被进一步抑制，使其恢复为更静止的状态。因此，共同的结果为纳米材料可用作体内纤维化治疗的潜在治疗抑制剂铺平了新途径。

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Inorganic Nanomaterials as Highly Efficient Inhibitors of Cellular Hepatic Fibrosis

Chronic liver dysfunction usually begins with hepatic fibrosis. To date, no effective anti-fibrotic drugs have been approved for clinical use in humans. In the current work, titanium dioxide (TiO₂) nanoparticles (NPs) and silicon dioxide (SiO₂) NPs are used as active inhibitors with intrinsic chemico-physico properties to block fibrosis and the associated phenotypes through acting on hepatic stellate cells (HSCs, the liver machinery for depositing scar tissues seen in fibrosis). Using LX-2 cells as the HSC model, internalized nanomaterials are found to suppress classical outcomes of cellular fibrosis, for example, inhibiting the expression of collagen I (Col-I) and alpha smooth muscle actin (α-SMA), initiated by transforming growth factor β (TGF-β)-activated HSCs in both a concentration-dependent and a time-dependent manner. Biochemically, these nanomaterials could also facilitate the proteolytic breakdown of collagen by up-regulation of matrix metalloproteinases (MMPs) and down-regulation of tissue inhibitors of MMPs (TIMPs). Furthermore, through regulating epithelial–mesenchymal transition (EMT) genes [e.g., E-cadherin (E-Cad) and N-cadherin (N-Cad)], the adhesion and migration profiles of TGF-β-activated LX-2 cells treated with nanomaterials were further inhibited, reverting them to a more quiescent state. Thus, the collective results pave the new way that nanomaterials can be used as potential therapeutic inhibitors for the treatment of in vivo fibrosis.

更新日期：2018-08-29

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