Li Yunxian, Chen Aoke, Hong An, Xiong Sheng, Chen Xiaojia, Xie Qiuling
College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China.
Bioengineering (Basel). 2024 Jul 9;11(7):693. doi: 10.3390/bioengineering11070693.
Corneal neovascularization is a significant cause of vision loss, often resulting in corneal clouding and chronic inflammation. Shark cartilage is widely recognized as a significant natural source of anti-angiogenic compounds. Our previous studies have shown that a polypeptide from white-spotted catshark ( Bonnet) has the potential to inhibit the angiogenesis of breast tumors. This study applied this peptide (SAIF) to a corneal alkali injury model to assess its effect on corneal neovascularization. Results revealed that SAIF inhibits endothelial cell proliferation, migration, and tube formation. SAIF inhibited VEGF-induced angiogenesis in the matrigel plug. Using the corneal alkali injury model, SAIF significantly inhibited corneal vascular neovascularization in mice. We found that SAIF not only significantly inhibited the upregulation of pro-angiogenic factors such as VEGF, bFGF, and PDGF expression induced by alkali injury, but also promoted the expression of anti-angiogenesis factor PEDF. Moreover, we also analyzed the MMPs and TIMPs involved in extracellular matrix (ECM) remodeling, angiogenesis, and lymphangiogenesis. We found that SAIF treatment inhibited the expression of pro-angiogenic factors like MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14, and promoted the expression of anti-angiogenesis factors such as MMP7, TIMP1, TIMP2, and TIMP3. In conclusion, SAIF acts as an anti-angiogenic factor to inhibit the proliferation, migration, and tube formation of endothelial cells, inhibit pro-angiogenic factors, promote anti-angiogenic factors, and regulate the expression of MMPs, ultimately inhibiting corneal neovascularization.
角膜新生血管形成是视力丧失的一个重要原因，常常导致角膜混浊和慢性炎症。鲨鱼软骨被广泛认为是抗血管生成化合物的一个重要天然来源。我们之前的研究表明，白斑猫鲨（Bonnet）的一种多肽有抑制乳腺肿瘤血管生成的潜力。本研究将这种肽（SAIF）应用于角膜碱烧伤模型，以评估其对角膜新生血管形成的影响。结果显示，SAIF抑制内皮细胞增殖、迁移和管腔形成。SAIF抑制基质胶栓中VEGF诱导的血管生成。利用角膜碱烧伤模型，SAIF显著抑制小鼠角膜血管新生。我们发现，SAIF不仅显著抑制碱烧伤诱导的促血管生成因子如VEGF、bFGF和PDGF表达的上调，还促进抗血管生成因子PEDF的表达。此外，我们还分析了参与细胞外基质（ECM）重塑、血管生成和淋巴管生成的基质金属蛋白酶（MMPs）和组织金属蛋白酶抑制剂（TIMPs）。我们发现，SAIF处理抑制促血管生成因子如MMP1、MMP2、MMP3、MMP9、MMP13和MMP14的表达，并促进抗血管生成因子如MMP7、TIMP1、TIMP2和TIMP3的表达。总之，SAIF作为一种抗血管生成因子，抑制内皮细胞的增殖、迁移和管腔形成，抑制促血管生成因子，促进抗血管生成因子，并调节MMPs的表达，最终抑制角膜新生血管形成。
