The involvement of integrin β1 signaling in the migration and myofibroblastic differentiation of skin fibroblasts on anisotropic collagen-containing nanofibers.
The involvement of integrin β1 signaling in the migration and myofibroblastic differentiation of skin fibroblasts on anisotropic collagen-containing nanofibers.
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DOI：
10.1016/j.biomaterials.2011.11.025
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发表时间：
2012-02
期刊：
影响因子：
14
通讯作者：
Wang, Hongjun
中科院分区：
文献类型：
--
作者：
Huang, Chengyang;Fu, Xiaoling;Liu, Jie;Qi, Yanmei;Li, Shaohua;Wang, Hongjun
关键词：
由于纳米纤维基质在形态和尺寸上与天然细胞外基质（ECM）相似，因此在皮肤伤口修复中具有很大的应用前景。了解各种纳米纤维基质如何调节皮肤细胞行为和细胞内信号通路，对于调节组织工程皮肤移植物的功能和影响伤口愈合过程非常重要。本研究通过免疫染色、迁移实验和分子分析研究了正常人真皮成纤维细胞（NHDFs）在含胶原纳米纤维基质上的表型表达，这些纳米纤维基质具有各向同性（即随机收集的纤维没有排列）或各向异性（即收集的纤维有排列）纤维组织。结果表明，两种纳米纤维基质对NHDFs的附着和生长具有相似的支持作用，但细胞形态不同，黏附灶的形成和分布有明显差异。各向异性纳米纤维显著触发了NHDFs中的整合素β1信号通路，其证据是活性整合素β1 （130 kD成熟形态）的增加和局灶粘附激酶（FAK）在tyr3 -397位点的磷酸化。各向异性基质也促进了NHDFs沿纤维的迁移，而整合素β1活性的中和消除了这种促进作用。此外，在各向异性纳米纤维基质上培养48小时后，NHDFs的成纤维细胞向肌成纤维细胞的分化能力大大增强。通过中和抗体抑制细胞整合素β1活性消除了这种增强。这些发现提示了整合素β1信号通路在调节纳米纤维诱导的成纤维细胞表型改变中的重要作用，并为含胶原纳米纤维基质在皮肤再生中的可能应用提供了深刻的理解。
Utilization of nanofibrous matrices for skin wound repair holds great promise due to their morphological and dimensional similarity to native extracellular matrix (ECM). It becomes highly desired to understand how various nanofibrous matrices regulate skin cell behaviors and intracellular signaling pathways, important to tuning the functionality of tissue-engineered skin grafts and affecting the wound healing process. In this study, the phenotypic expressions of normal human dermal fibroblasts (NHDFs) on collagen-containing nanofibrous matrices with either isotropic (i.e., fibers collected randomly with no alignment) or anisotropic (i.e., fibers collected with alignment) fiber organizations were studied by immunostaining, migration assay and molecular analyses. Results showed that both nanofibrous matrices supported the attachment and growth of NHDFs similarly, while showing different cell morphology with distinct variation in focal adhesion formation and distribution. Anisotropic nanofibers significantly triggered the integrin β1 signaling pathway in NHDFs as evidenced by an increase of active integrin β1 (130 kD mature form) and phosphorylation of focal adhesion kinase (FAK) at Tyr-397. Anisotropic matrices also promoted the migration of NHDFs along the fibers, while neutralization of the integrin β1 activity abolished this promotion. Moreover, the fibroblast-to-myofibroblast differentiation was greatly enhanced for the NHDFs cultured on anisotropic nanofibrous matrices over a period of 48 hours. Inhibition of cellular integrin β1 activity by neutralizing antibody eliminated this enhancement. These findings suggest the important role of integrin β1 signaling pathway in regulating the nanofiber-induced fibroblast phenotypic alteration and providing insightful understanding of the possible application of collagen-containing nanofibrous matrices for skin regeneration.
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影响因子：
14
作者：
Eisenbarth, E;Meyle, J;Breme, J
通讯作者：
Breme, J
影响因子：
--
作者：
Ma, ZW;Kotaki, M;Ramakrishna, S
通讯作者：
Ramakrishna, S
影响因子：
4
作者：
Ng, CP;Hinz, B;Swartz, MA
通讯作者：
Swartz, MA
影响因子：
--
作者：
Dalby, MJ;Di Silvio, L;Bonfield, W
通讯作者：
Bonfield, W
影响因子：
7.5
作者：
Mitra, Satyajit K.;Schlaepfer, David D.
通讯作者：
Schlaepfer, David D.