State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010021, China.
Int J Mol Sci. 2023 Jul 7;24(13):11198. doi: 10.3390/ijms241311198.
Dermal papilla cells (DPCs) cultured in vitro induce hair follicle formation. Using a hypoxic microenvironment to culture adipose mesenchymal stem cells (ADSCs) can promote hair follicle growth. However, the exact molecular mechanisms underlying this process remain unclear. In this study, ADSCs and DPCs from Arbas Cashmere goats were used. A hypoxic microenvironment promoted the proliferation of ADSCs and increased the pluripotency of ADSCs. The growth factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) were upregulated in ADSCs in the hypoxia-conditioned medium (Hypo-cm). Hypo-cm also enhanced the ability of DPCs to induce hair follicle formation. Inhibitors of the ERK1/2 signaling pathway caused the expressions of growth factors that increased in hypoxic microenvironments to decrease; moreover, hypoxia-inducible factor-1α () increased the expression levels of VEGF, bFGF, and PDGF and inhibited the expression of bone morphogenic protein 7 (). In conclusion, these findings improve the theoretical basis for the development of gene therapy drugs for the treatment of alopecia areata and hair thinning.
真皮乳头细胞(DPCs)在体外培养可诱导毛囊形成。利用低氧微环境培养脂肪间充质干细胞(ADSCs)可促进毛囊生长。然而,这一过程的确切分子机制尚不清楚。本研究使用 Arbas 绒山羊的 ADSCs 和 DPCs。低氧微环境促进了 ADSCs 的增殖,并增加了 ADSCs 的多能性。缺氧条件培养基(Hypo-cm)中血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)和血小板衍生生长因子(PDGF)等生长因子的表达上调。Hypo-cm 还增强了 DPCs 诱导毛囊形成的能力。ERK1/2 信号通路抑制剂导致低氧微环境中增加的生长因子表达减少;此外,缺氧诱导因子-1α()增加了 VEGF、bFGF 和 PDGF 的表达水平,并抑制了骨形态发生蛋白 7()的表达。总之,这些发现为治疗斑秃和头发稀疏的基因治疗药物的开发提供了理论基础。