Bentov Itay, Damodarasamy Mamatha, Plymate Stephen, Reed May J
Department of Anesthesiology and Pain Medicine, Harborview Medical Center, University of Washington, Box 359724, 325 Ninth Avenue, Seattle, WA, 98104, USA,
Biogerontology. 2014 Aug;15(4):329-37. doi: 10.1007/s10522-014-9501-8. Epub 2014 Apr 26.
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.
皮肤老化会导致受伤易感性增加以及伤口愈合受损。老年真皮中成纤维细胞的增殖减少，这导致伤口闭合延迟。年龄相关差异部分受局部或全身因素调节，如胰岛素样生长因子-1/胰岛素样生长因子1受体（IGF-1/IGF1R）系统。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在更好模拟体内真皮细胞外基质的三维胶原基质中增殖能力的改变相关。测量了年轻和老年人类真皮成纤维细胞在三维胶原中的增殖及其与IGF1R表达基线水平的关联。确定了刺激和抑制细胞外信号调节激酶（Erk）磷酸化对三维胶原基质中成纤维细胞增殖能力的影响。我们的结果表明，相对于年轻成纤维细胞，老年真皮成纤维细胞的增殖和Erk磷酸化减少。老年成纤维细胞中Erk磷酸化的激活与三维胶原中成纤维细胞增殖的显著增加相关。
