毛囊真皮鞘细胞中过表达Noggin对皮肤及毛囊生长的作用

Effect of Noggin overexpression in hair follicle dermal sheath cells on the growth of skin and hair follicles

背景:Noggin蛋白是一个抑制BMP信号通路的重要分子,可以与BMP2/4结合形成复合物,从而阻断BMP信号,影响生物有机体的正常发育过程。研究认为真皮鞘细胞是一类能够长期自我更新的真皮干细胞,参与毛囊再生过程中真皮毛乳头和真皮鞘的形成。在毛囊发育过程中,真皮毛乳头中Noggin参与毛囊的起始,Noggin的缺失会导致毛囊数量的减少和毛囊生长缓慢,但人们对于Noggin蛋白在毛囊真皮鞘中的作用所知甚少。目的:研究Noggin蛋白在毛囊真皮鞘中的生物学功能。方法:利用真皮鞘特异的αSMA-Cre ERT2工具鼠在真皮鞘中特异过表达Noggin蛋白,分别在出生后8,9 d对实验组αSMA-CreER;pMES-Noggin小鼠和对照组αSMA-CreER小鼠注射4-羟基他莫昔芬,在出生后21,23,28 d获取皮肤组织,苏木精-伊红染色观察毛囊生长情况和皮下脂肪层厚度,免疫组化染色分析表型。结果与结论:通过苏木精-伊红染色结果发现毛囊生长并没有受到影响,但毛囊皮下脂肪组织生长发育受到严重影响,小鼠皮下脂肪层变薄。免疫组化结果说明BMP信号降低可能是导致毛囊脂肪层变薄的原因。这一发现拓展了人们对于真皮鞘细胞和Noggin蛋白的认识,也为人们更加准确理解毛囊再生和组织生长机制提供了重要依据。

BACKGROUND:Noggin is an inhibitory molecule of bone morphogenetic protein(BMP)signaling,which can bind to BMP2/4 to form a complex,thereby blocking BMP signaling and affecting normal development.Some studies have suggested that dermal sheath cells are a kind of dermal stem cells that can self-renew for a long time,and participate in the formation of dermal papilla and dermal sheath during hair follicle regeneration.During the development of hair follicles,Noggin is involved in the induction of hair follicle regeneration,and its loss leads to a decrease in hair follicle number and slows hair follicle growth.However,little is known about the Noggin in the study of hair follicle dermal sheaths.OBJECTIVE:To study the biological function of Noggin protein in the dermal sheath of hair follicles.METHODS:The dermal sheath specificα-SMA-Cre ERT2 tool mice were used to specifically overexpress Noggin protein in the dermal sheath.At 8 and 9 days after birth,αSMA-CreER;pMES-Noggin mice in the experimental group andαSMA-CreER mice in the control group were injected with 4-hydroxytamoxifen.At 21,23,and 28 days after birth,mouse skin tissues were obtained.Hematoxylin-eosin staining was used to observe hair follicle growth and subcutaneous fat layer thickness,and immunohistochemical staining was used to analyze cell phenotype.RESULTS AND CONCLUSION:Based on the findings of hematoxylin-eosin staining,we found that the growth of hair follicle was not affected,but the growth and development of subcutaneous adipose tissue of hair follicles were seriously impacted,presenting with the subcutaneous fat layer becoming thinned.The immunohistochemical results indicated that the decrease of BMP signaling may result in the thinning of the hair follicle fat layer.This discovery expands the understanding of dermal sheath cells and Noggin protein,and provides an important basis for more accurate understanding of hair follicle regeneration and tissue growth mechanisms.