Oxidative stress-induced premature dermal papilla aging impairs hair follicle epithelial-mesenchymal interaction
Date Issued
2014
Date
2014
Author(s)
Huang, Yi-Ching
Abstract
Hair follicle (HF) is composed of epithelium and mesenchyme. The dermal papilla (DP) is a component of HF mesenchyme and it is involved in the development, growth, cycle regulation, shape, and organ of hair. References showed DP can educate the undifferentiated epithelia cells going to follicular fate and induce ectopic hair neogenesis in adult skin. During HF morphogenesis, DP cells are from fibroblasts (FB), uncharacterized mesenchyme. DP and FB are derived from the same original mesencyme and shared the most genes. However, amputated DP could be regenerated from local fibroblast. There are many studies that have shown that radiotherapy and chemotherapy-induced hair dystrophy and even hair loss is associated with follicular epithelial damage. However, there is little literature on the damage of follicular mesenchyme. To address this question, we found that fibroblasts become more resistant to environmental stress when they differentiate into DP cells. DP cells had higher survival than FB under oxidative stress according to induce cleaved caspase 3, induce cell death, and gamma-H2A.X in FB. DP cells had higher bcl-2, anti-apoptotic factor, expression than FB. DP after radiation can still proliferate but FB can’t. However, DP cells have greater resistant ability to stress than fibroblasts.
Permanent chemotherapy-induced alopecia had diffuse thinning hair. Previous studies have showed that balding DP cells from androgenetic alopecia (AGA) have smaller cell size and limited proliferation compared to non-balding DP cells. Many evidences show that premature senescence is a characteristic of balding DP cells. The exhaustive pathological mechanism is yet unclear. However, the problem is, it difficult to expand numerous balding or aged DP cells in culture. We found the survival DP cells tend to become senescence after oxidative stress. Aged DP cells became enlarged and flatness, having the limited proliferating ability and increasing senescence-associated beta galactosidase activity, p16 and p21. However, the oxidative stress induce senescence wasn’t happened in FB cells. These senescent DP cells conserved the DP specific genes. We suggested that the epithelium to mesenchyme signaling was impaired according to the senescent DP cells are irreversibly by keratinocyte conditioned medium. The HF inductive genes, akp and versican, were decreased in senescent DP cells. The senescent DP cells had less AKP activity and impaired self-aggregated ability. Importantly, they lost the HF induction ability. We also found that the senescent DP cells unable to stimulate HF keratinocytes (KC) growth and support clonal growth and stemness of HF keratinocytes. The senescent DP cells exhibited uredced ability to induce follicular differentiation. We suggested that the mesenchyme to epithelium signaling and stem cell activation were impaired. Base on screen of microarray and cytokine array, we found that the interleukins were up-regulated in senescent DP medium, especially in interleukin 6 (IL-6). The senescent DP cells inhibit of KC clonal growth and stem cell activation by induced IL-6 secretion.
The DP plays a crucial role of controlling HF organ size. In our observation, we found that the DP cell number is correlated with HF thickness and is statistically significant. We purpose to control the size of regenerated hair follicles through tissue engineering. According to our previous results, the adhesivity and aggregation ability of DP cells can be controlled by different substratum hydrophobicity. We found that the DP cells could format DP spheroids at different sizes when cultured in polyvinyl alcohol (PVA)-coating plate by different cell densities. The advantages are rapid and to ensure that they are injectable. Characters of spheroidal microtissues obtained on PVA-coated surface. We found that larger DP spheroids showed higher HF induction efficiency but size of preformed DP spheroids did not affect the thickness of regenerated hair.
In our studies, we set up a model of rapid and easy senescent DP cells acquisition to elucidate the role of senescent mesenchyme in the interaction of epithelium and mesenchyme for other organs. This model is a beneficial strategy to explore the pathological mechanism of organ atrophy as a result of oxidative stress or aging.
Subjects
毛囊真皮乳突細胞
皮膚纖維母細胞
老化
表皮-真皮交互作用
毛囊再生
Type
thesis
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