Mouse skin fibroblasts with mesenchymal stem cell marker p75 neurotrophin receptor proliferate in response to prolyl-hydroxyproline
Mouse skin fibroblasts with mesenchymal stem cell marker p75 neurotrophin receptor proliferate in response to prolyl-hydroxyproline
复制标题
DOI：
10.1016/j.jff.2020.103792
复制
发表时间：
2020-03-01
影响因子：
5.6
通讯作者：
Sato, Kenji
中科院分区：
文献类型：
--
作者：
Asai, Tomoko T.;Yoshikawa, Kazunobu;Sato, Kenji
脯氨酰-羟脯氨酸（Pro-Hyp）水平在人血液中增加，并触发贴附在胶原蛋白上的原代培养成纤维细胞的增殖。这种增殖作用与胶原水解物摄取的有益作用有关，包括促进伤口愈合。然而，一些成纤维细胞系不响应Pro-Hyp。在这项研究中，我们专注于间充质干细胞标志物p75神经营养因子受体（p75 NTR），因为p75 NTR阳性细胞在伤口愈合部位增加。从解剖的小鼠皮肤迁移1-4天的大多数成纤维细胞表达p75 NTR。然而，经过长期培养，p75 NTR阳性成纤维细胞的比例下降。特异性掺入异硫氰酸荧光素（FITC）标记的Pro-Hyp和Pro-Hyp的p75 NTR阳性成纤维细胞显著增加在胶原凝胶上生长的p75 NTR阳性成纤维细胞的数量。这些结果表明Pro-Hyp可以通过刺激伤口愈合部位的p75 NTR阳性成纤维细胞来促进伤口愈合，而它对正常组织中p75 NTR阴性的常驻成纤维细胞几乎没有影响。
Prolyl-hydroxyproline (Pro-Hyp) levels increase in human blood on ingesting collagen hydrolysate and trigger proliferation of primary cultured fibroblasts attached on collagen. Such proliferative effects have been associated with the beneficial effects of collagen hydrolysate ingestion including enhancement of wound healing. However, some fibroblast cell lines do not respond to Pro-Hyp. In this study, we focused on the mesenchymal stem cell marker p75 neurotrophin receptor (p75NTR), because p75NTR-positive cells are increased at wound healing sites. Most fibroblasts that had migrated from the dissected mouse skin for 1-4 days expressed p75NTR. After prolonged cultivation, however, the ratio of p75NTR-positive fibroblasts dropped. The p75NTR-positive fibroblasts specifically incorporated fluorescein isothiocyanate (FITC)-labeled Pro-Hyp and Pro-Hyp significantly increased the number of p75NTR-positive fibroblasts grown on collagen gel. These results suggest that Pro-Hyp could enhance wound healing by stimulating p75NTR-positive fibroblasts at wound healing sites, while it has little effect on p75NTR-negative resident fibroblasts in normal tissues.