膜联蛋白 A1 通过 EGF 信号通路影响小鼠毛囊生长。

ANXA1 affects murine hair follicle growth through EGF signaling pathway.

机构信息

State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, Inner Mongolia 010070, China.

Central Lab of Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

出版信息

Gene. 2021 Mar 1;771:145343. doi: 10.1016/j.gene.2020.145343. Epub 2020 Dec 14.

DOI:10.1016/j.gene.2020.145343

PMID:33333231

Abstract

Annexin A1 (ANXA1), a calcium-dependent phospholipid binding protein expressed in animals, plants and microorganisms, participates in various cellular physiological activities. Previous proteomics analysis indicates that the level of ANXA1 in mice dorsal skin changes during hair growth cycle, we speculate that ANXA1 may play an important role in hair follicle (HF) development. Thus, Anxa1 knock-out (KO) and over-expression (OE) mice were constructed to test its function. Our results showed that in addition to the diameter of HF and hair shaft, ANXA1 could participate in hair growth by affecting the density of HF, and the proliferation of hair follicle stem cells (HFSCs). Meanwhile, molecular analysis showed that EGF signaling pathway is involved in the function of ANXA1. The expression of Anxa1 is negatively correlated with the levels of Egf, Notch1, Mkk7, and phosphorylated AKT1 and ERK/2 proteins. The levels of Egf, Notch1, Mkk7 and phosphorylation of AKT1 and ERK/2 increased in Anxa1 KO mice but decreased in Anxa1 OE mice. Taken together, our results suggested that ANXA1 could affect the hair growth by regulating the HFSCs proliferation through EGF signaling pathway.

摘要

膜联蛋白 A1（ANXA1）是一种在动物、植物和微生物中表达的钙依赖性磷脂结合蛋白，参与多种细胞生理活动。先前的蛋白质组学分析表明，在毛发生长周期中，小鼠背部皮肤的 ANXA1 水平发生变化，我们推测 ANXA1 可能在毛囊（HF）发育中发挥重要作用。因此，构建了 Anxa1 敲除（KO）和过表达（OE）小鼠以测试其功能。我们的结果表明，除了 HF 和毛干的直径外，ANXA1 还可以通过影响 HF 的密度和毛囊干细胞（HFSCs）的增殖来参与毛发生长。同时，分子分析表明，EGF 信号通路参与了 ANXA1 的功能。Anxa1 的表达与 Egf、Notch1、Mkk7 和磷酸化 AKT1 和 ERK/2 蛋白的水平呈负相关。Anxa1 KO 小鼠中 Egf、Notch1、Mkk7 和磷酸化 AKT1 和 ERK/2 的水平增加，而 Anxa1 OE 小鼠中则减少。总之，我们的结果表明，ANXA1 可以通过 EGF 信号通路调节 HFSCs 的增殖来影响毛发生长。