Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi, 487-8501, Japan.
Cytotechnology. 2015 Aug;67(4):609-20. doi: 10.1007/s10616-014-9707-2. Epub 2014 Mar 4.
Although it has been reported that levels of hyaluronan are decreased in the dermis of aged skin, little is known about the cellular mechanism(s) underlying that hyaluronan deficiency. Since hyaluronan is produced by dermal fibroblasts and is secreted into the surrounding dermal tissues, we examined the secretion of hyaluronan by dermal fibroblasts and characterized its cellular mechanism using real-time RT-PCR and western blotting for its synthesizing and degrading enzymes, hyaluronan synthase and hyaluronidase, respectively. The secretion of hyaluronan by dermal fibroblasts derived from differently aged human donors, was higher in the younger human fibroblasts tested (0 and 19 years old) compared to the older human fibroblasts tested (39, 56 and 77 years old). The relative secretion levels of hyaluronan by the different human fibroblasts tested were attributable to the relative expression of hyaluronan synthases 1, 2, 3 but not hyaluronidases 1, 2 enzymes at the gene and protein levels among those fibroblasts. These findings indicate that the deficiency of hyaluronan in the aged dermis might result from the down-regulation in the potential of older human fibroblasts to secrete hyaluronan and that decrease in secretory potential is mainly associated with the down-regulated expression of hyaluronan synthases, especially hyaluronan synthase 2, but not with the expression levels of hyaluronidases.
虽然已有报道称，衰老皮肤真皮层中的透明质酸水平降低，但对于导致透明质酸缺乏的细胞机制知之甚少。由于透明质酸是由真皮成纤维细胞产生并分泌到周围的真皮组织中，我们通过实时 RT-PCR 和 Western blot 检测了真皮成纤维细胞分泌透明质酸的情况，并分别用其合成酶和降解酶（透明质酸合成酶和透明质酸酶）对其细胞机制进行了特征分析。来自不同年龄供体的真皮成纤维细胞分泌的透明质酸，在年轻的供体（0 岁和 19 岁）中比在年龄较大的供体（39 岁、56 岁和 77 岁）中更高。不同供体的真皮成纤维细胞分泌的透明质酸的相对水平归因于这些成纤维细胞中透明质酸合成酶 1、2、3 的相对表达，而不是透明质酸酶 1、2 的相对表达。这些发现表明，衰老真皮中透明质酸的缺乏可能是由于老年成纤维细胞分泌透明质酸的能力下降所致，而分泌能力的下降主要与透明质酸合成酶，尤其是透明质酸合成酶 2 的表达下调有关，而与透明质酸酶的表达水平无关。
