Decreased proliferative capacity of aged dermal fibroblasts in a three dimensional matrix is associated with reduced IGF1R expression and activation.

Decreased proliferative capacity of aged dermal fibroblasts in a three dimensional matrix is associated with reduced IGF1R expression and activation.
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DOI:
10.1007/s10522-014-9501-8
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发表时间:
2014-08
期刊:
影响因子:
4.5
通讯作者:
Reed, May J.
Reed, May J.
中科院分区:
医学3区
文献类型:
--
作者:
Bentov, Itay;Damodarasamy, Mamatha;Plymate, Stephen;Reed, May J.

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皮肤老化会增加受伤的可能性并损害伤口愈合。老化真皮中成纤维细胞的增殖减少,这导致伤口闭合延迟。与年龄相关的差异部分受到局部或全身因素(例如 IGF-1/IGF1R 系统)的调节。本研究的目的是确定与年轻成纤维细胞相比,老年人类真皮成纤维细胞中 IGF1R 的表达和激活是否与更好地模拟体内真皮细胞外基质的 3D 胶原基质的增殖能力改变相关。测量了年轻和老年人类真皮成纤维细胞在 3D 胶原中的增殖及其与 IGF1R 表达基线水平的关系。定义了刺激和抑制 Erk 磷酸化对 3D 胶原基质中成纤维细胞增殖能力的影响。我们的结果表明,相对于年轻的成纤维细胞,衰老的真皮成纤维细胞的增殖和 Erk 磷酸化减少。老化成纤维细胞中 Erk 磷酸化的激活与 3D 胶原中成纤维细胞增殖的显着增加相关。
Skin aging results in increased susceptibility to injury and impaired wound healing. Proliferation of fibroblasts is reduced in aged dermis, which contributes to delays in wound closure. Age-associated differences are regulated, in part, by local or systemic factors such as the IGF-1/IGF1R system. The aim of this study was to determine if expression and activation of IGF1R in aged human dermal fibroblasts, when compared to young fibroblasts, is associated with altered proliferative capacity in a 3D collagen matrix that better simulates the dermal extracellular matrix in vivo. The proliferation of young and aged human dermal fibroblasts in 3D collagen and its association with baseline levels of IGF1R expression were measured. The effect of stimulation and inhibition of Erk phosphorylation on the proliferative capacity of fibroblasts in a 3D collagen matrix was defined. Our results show that proliferation and Erk phosphorylation is reduced in aged dermal fibroblasts relative to young fibroblasts. Activation of Erk phosphorylation in aged fibroblasts is associated with a significant increase in fibroblast proliferation in 3D collagen.
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