Substrate Stiffness Combined with Hepatocyte Growth Factor Modulates Endothelial Cell Behavior.
Substrate Stiffness Combined with Hepatocyte Growth Factor Modulates Endothelial Cell Behavior.
复制标题
基质硬度与肝细胞生长因子相结合调节内皮细胞行为
DOI：
10.1021/acs.biomac.6b00318
复制
发表时间：
2016-09-12
影响因子：
6.2
通讯作者：
Ji, Jian
中科院分区：
文献类型：
--
作者：
Chang, Hao;Liu, Xi-qiu;Hu, Mi;Zhang, He;Li, Bo-chao;Ren, Ke-feng;Boudou, Thomas;Albiges-Rizo, Corinne;Picart, Catherine;Ji, Jian
内皮细胞在调节各种生理和病理过程中起着至关重要的作用。内皮细胞的行为受到物理因素(例如底物硬度)和生化因素(例如生长因子)的调节。然而，这些线索对EC行为的协同影响很少被研究。在本研究中，我们构建了不同硬度的聚L赖氨酸/透明质酸多层膜，并将其暴露于含有和不含有肝细胞生长因子的培养液中。我们发现内皮细胞的黏附、迁移和增殖与基质硬度呈正相关，并且HGF进一步促进了这些行为。有趣的是，低硬度基质上的内皮细胞在迁移和增殖方面对HGF表现出更强的反应，这表明HGF可以深刻地影响与EC生长相关的硬度依赖的EC行为。在EC单层形成后，通过单层完整性、一氧化氮产生和内皮型一氧化氮合酶基因表达来评价与内皮功能相关的EC行为。我们首次证明内皮功能与基质硬度呈负相关。尽管HGF改善了内皮功能，但HGF不能改变内皮功能的僵硬依赖方式。综上所述，这项研究为深入了解物理和生化线索对EC行为的协同影响提供了见解，并为基于EC的再生医学开发优化生物材料提供了巨大的潜力。
Endothelial cells (ECs) play a crucial role in regulating various physiological and pathological processes. The behavior of ECs is modulated by physical (e.g., substrate stiffness) and biochemical cues (e.g., growth factors). However, the synergistic influence of these cues on EC behavior has rarely been investigated. In this study, we constructed poly(L-lysine)/hyaluronan (PLL/HA) multilayer films with different stiffness and exposed ECs to these substrates with and without hepatocyte growth factor (HGF)-supplemented culture medium. We demonstrated that EC adhesion, migration, and proliferation were positively correlated with substrate stiffness and that these behaviors were further promoted by HGF. Interestingly, ECs on the lower stiffness substrates showed stronger responses to HGF in terms of migration and proliferation, suggesting that HGF can profoundly influence stiffness-dependent EC behavior correlated with EC growth. After the formation of an EC monolayer, EC behaviors correlated with endothelial function were evaluated by characterizing monolayer integrity, nitric oxide production, and gene expression of endothelial nitric oxide synthase. For the first time, we demonstrated that endothelial function displayed a negative correlation with substrate stiffness. Although HGF improved endothelial function, HGF was not able to change the stiffness-dependent manner of endothelial functions. Taken together, this study provides insights into the synergetic influence of physical and biochemical cues on EC behavior and offers great potential in the development of optimized biomaterials for EC based regenerative medicine.
登录
查看更多内容
影响因子：
3.1
作者：
Birukova, Anna A.;Tian, Xinyong;Cokic, Ivan;Beckham, Yvonne;Gardel, Margaret L.;Birukov, Konstantin G.
通讯作者：
Birukov, Konstantin G.
影响因子：
4.9
作者：
Ataollahi, Forough;Pramanik, Sumit;Abu Osman, Noor Azuan
通讯作者：
Abu Osman, Noor Azuan
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW
影响因子：
14
作者：
Brewster, Luke P.;Bufallino, Dominick;Greisler, Howard P.
通讯作者：
Greisler, Howard P.
影响因子：
14
作者：
Chen, Alice A.;Khetani, Salman R.;Lee, Sunyoung;Bhatia, Sangeeta N.;Van Vliet, Krystyn J.
通讯作者：
Van Vliet, Krystyn J.