真皮脂肪组织分泌 HGF 以促进人类头发生长和色素沉着。

Dermal Adipose Tissue Secretes HGF to Promote Human Hair Growth and Pigmentation.

机构信息

Centre for Dermatology Research, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester, United Kingdom; Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA; Department of Materials, Henry Royce Institute, University of Manchester, Manchester, United Kingdom.

出版信息

J Invest Dermatol. 2021 Jul;141(7):1633-1645.e13. doi: 10.1016/j.jid.2020.12.019. Epub 2021 Jan 23.

DOI:10.1016/j.jid.2020.12.019

PMID:33493531

Abstract

Hair follicles (HFs) are immersed within dermal white adipose tissue (dWAT), yet human adipocyte‒HF communication remains unexplored. Therefore, we investigated how perifollicular adipocytes affect the physiology of human anagen scalp HFs. Quantitative immunohistomorphometry, X-ray microcomputed tomography, and transmission electron microscopy showed that the number and size of perifollicular adipocytes declined during anagen‒catagen transition, whereas fluorescence-lifetime imaging revealed increased lipid oxidation in adipocytes surrounding the bulge and/or sub-bulge region. Ex vivo, dWAT tendentially promoted hair shaft production, and significantly stimulated hair matrix keratinocyte proliferation and HF pigmentation. Both dWAT pericytes and PREF1/DLK1 adipocyte progenitors secreted HGF during human HF‒dWAT co-culture, for which the c-Met receptor was expressed in the hair matrix and dermal papilla. These effects were reproduced using recombinant HGF and abrogated by an HGF-neutralizing antibody. Laser-capture microdissection‒based microarray analysis of the hair matrix showed that dWAT-derived HGF upregulated keratin (K) genes (K27, K73, K75, K84, K86) and TCHH. Mechanistically, HGF stimulated Wnt/β-catenin activity in the human hair matrix (increased AXIN2, LEF1) by upregulating WNT6 and WNT10B, and inhibiting SFRP1 in the dermal papilla. Our study demonstrates that dWAT regulates human hair growth and pigmentation through HGF secretion, and thus identifies dWAT and HGF as important novel molecular and cellular targets for therapeutic intervention in human hair growth and pigmentation disorders.

摘要

毛囊（HFs）沉浸在真皮白色脂肪组织（dWAT）中，但人类脂肪细胞与 HF 的通讯仍未被探索。因此，我们研究了毛囊周围脂肪细胞如何影响人类生长期头皮 HF 的生理学。定量免疫组织形态计量学、X 射线微计算机断层扫描和透射电子显微镜显示，在生长期到退行期的过渡期间，毛囊周围脂肪细胞的数量和大小减少，而荧光寿命成像显示围绕隆起和/或亚隆起区域的脂肪细胞的脂质氧化增加。在体外，dWAT 倾向于促进头发轴的产生，并显著刺激毛囊基质角质形成细胞的增殖和 HF 色素沉着。dWAT 周细胞和 PREF1/DLK1 脂肪细胞祖细胞在人 HF-dWAT 共培养期间分泌 HGF，c-Met 受体在毛发基质和真皮乳头中表达。在人 HF-dWAT 共培养中，使用重组 HGF 复制了这些作用，并使用 HGF 中和抗体阻断了这些作用。基于激光捕获微切割的毛发基质微阵列分析显示，dWAT 衍生的 HGF 上调了角蛋白（K）基因（K27、K73、K75、K84、K86）和 TCHH。从机制上讲，HGF 通过上调 WNT6 和 WNT10B 并抑制真皮乳头中的 SFRP1 来刺激人毛发基质中的 Wnt/β-catenin 活性（增加 AXIN2、LEF1）。我们的研究表明，dWAT 通过 HGF 分泌调节人类头发生长和色素沉着，因此确定 dWAT 和 HGF 是治疗人类头发生长和色素沉着障碍的重要新的分子和细胞靶标。