Chen Jian, Fan Zhe-Xiang, Zhu De-Cong, Guo Yi-Long, Ye Ke, Dai Damao, Guo Zhi, Hu Zhi-Qi, Miao Yong, Qu Qian
Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, China.
Front Cell Dev Biol. 2021 Oct 15;9:728188. doi: 10.3389/fcell.2021.728188. eCollection 2021.
Hair follicle stem cells are extensively reprogrammed by the aging process, manifesting as diminished self-renewal and delayed responsiveness to activating cues, orchestrated by both intrinsic microenvironmental and extrinsic macroenvironmental regulators. Dermal white adipose tissue (dWAT) is one of the peripheral tissues directly adjacent to hair follicles (HFs) and acts as a critical macroenvironmental niche of HF. dWAT directly contributes to HF aging by paracrine signal secretion. However, the altered interrelationship between dWAT and HF with aging has not been thoroughly understood. Here, through microdissection, we separated dWAT from the skin of aged mice (18 months) and young mice (2 months) in telogen and depilation-induced anagen for transcriptome comparing. Notably, compared with young dWAT, aberrant inflammatory regulators were recapitulated in aging dWAT in telogen, including substantial overexpressed inflammatory cytokines, matrix metalloproteinases, and prostaglandin members. Nonetheless, with anagen initiation, inflammation programs were mostly abolished in aging dWAT, and instead of which, impaired collagen biosynthesis, angiogenesis, and melanin synthesis were identified. Furthermore, we confirmed the inhibitory effect on hair growth of CXCL1, one of the most significantly upregulated inflammation cytokines in aging dWAT. Besides this, we also identified the under-expressed genes related to Wnt signaling fibroblast growth factor family members and increased BMP signaling in aging dWAT, further unraveling the emerging role of dWAT in aging HFs malfunction. Finally, we proved that relieving inflammation of aging dWAT by injecting high-level veratric acid stimulated HF regenerative behavior in aged mice. Concomitantly, significantly decreased TNF-a, CCL2, IL-5, CSF2, and increased IL10 in dWAT was identified. Overall, the results elaborated on the complex physiological cycling changes of dWAT during aging, providing a basis for the potential regulatory effect of dWAT on aging HFs.
毛囊干细胞会因衰老过程而发生广泛的重编程，表现为自我更新能力下降以及对激活信号的反应延迟，这是由内在微环境和外在宏观环境调节因子共同调控的。真皮白色脂肪组织（dWAT）是与毛囊（HF）直接相邻的外周组织之一，是HF的关键宏观环境生态位。dWAT通过旁分泌信号分泌直接导致HF衰老。然而，随着衰老，dWAT与HF之间相互关系的变化尚未得到充分理解。在这里，通过显微切割，我们从处于休止期的老年小鼠（18个月）和年轻小鼠（2个月）以及脱毛诱导的生长期的皮肤中分离出dWAT，用于转录组比较。值得注意的是，与年轻的dWAT相比，休止期衰老的dWAT中出现了异常的炎症调节因子，包括大量过度表达的炎症细胞因子、基质金属蛋白酶和前列腺素成员。尽管如此，随着生长期的开始，衰老的dWAT中的炎症程序大多被消除，取而代之的是，发现了胶原蛋白生物合成、血管生成和黑色素合成受损。此外，我们证实了衰老的dWAT中上调最显著的炎症细胞因子之一CXCL1对毛发生长的抑制作用。除此之外，我们还在衰老的dWAT中鉴定出与Wnt信号、成纤维细胞生长因子家族成员相关的低表达基因以及增强的骨形态发生蛋白信号，进一步揭示了dWAT在衰老HF功能障碍中的新作用。最后，我们证明通过注射高剂量藜芦酸减轻衰老dWAT的炎症可刺激老年小鼠的HF再生行为。同时，还发现dWAT中肿瘤坏死因子-α、CCL2、白细胞介素-5、集落刺激因子2显著降低，白细胞介素10增加。总体而言，这些结果阐述了衰老过程中dWAT复杂的生理循环变化，为dWAT对衰老HF的潜在调节作用提供了依据。
