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地塞米松在介导 Wnt 拮抗剂 SFRP2 和 SFRP3 对人毛囊生长的矛盾作用中的作用。

The role of dexamethasone in mediating the contradictory effects of Wnt antagonists SFRP2 and SFRP3 on human hair follicle growth.

机构信息

Department of Immunology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-Ro, Jung-Gu, Daegu, 41944, Republic of Korea.

Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Republic of Korea.

出版信息

Sci Rep. 2023 Oct 2;13(1):16504. doi: 10.1038/s41598-023-43688-5.

Abstract

Stress can be one of the leading causes of hair loss. Stress related hormones, glucocorticoids (GCs), secretion by hair follicle have been mentioned in literature and proven to exert an inhibitory effect on hair follicle cells growth by modulating the expression of target genes related to cell proliferation and cycling. The gene modulating effect of the synthetic GC, dexamethasone (DEX), in human dermal papilla (DP) cells has been outlined in this study by mediating a contradictory effect on the expression of secreted frizzled related protein 2 (SFRP2) and SFRP3. The SFRP2 and SFRP3 possess a regulating effect on wnt signaling pathway. Their structural similarities to the cysteine-rich-domain of the frizzled receptors (FZD) allow their binding to the wnt ligands causing the blocking of the wnt ligands-receptors complex. The SFRP family members have been known as inhibitors of the wnt signaling modulating the proliferation and development of various cells. In hair follicle cells, SFRP2 activity has been reported positively on the proliferation of keratinocytes. However, the SFRP3 effect hasn't been well addressed. Under stress, the investigation of the mRNA and protein expressions of SFRP members in human DP cells revealed opposite expressions where SFRP2 decreased while SFRP3 increased by DEX. The proliferation rate of hair keratinocytes outer root sheath was detected via immunofluorescence highlighting the stimulatory effect of SFRP2 and the inhibitory effect of SFRP3. Here, we sought to determine the effect of GC agonist on SFRPs expression and their effect on hair follicle growth.

摘要

压力可能是导致脱发的主要原因之一。文献中提到,应激相关激素——糖皮质激素(GCs)的分泌会对毛囊细胞产生抑制作用,通过调节与细胞增殖和周期相关的靶基因的表达来实现。本研究通过介导对分泌卷曲相关蛋白 2(SFRP2)和 SFRP3 表达的相反作用,概述了合成 GC 地塞米松(DEX)对人真皮乳头(DP)细胞的基因调节作用。SFRP2 和 SFRP3 对 wnt 信号通路具有调节作用。它们与卷曲受体(FZD)富含半胱氨酸结构域的结构相似,允许它们与 wnt 配体结合,从而阻断 wnt 配体-受体复合物。SFRP 家族成员被认为是 wnt 信号的抑制剂,可调节各种细胞的增殖和发育。在毛囊细胞中,SFRP2 活性被报道可促进角质形成细胞的增殖。然而,SFRP3 的作用尚未得到很好的解决。在应激下,检测人 DP 细胞中 SFRP 成员的 mRNA 和蛋白表达,发现 SFRP2 降低而 SFRP3 增加,DEX 表达相反。通过免疫荧光检测外根鞘的毛发角质形成细胞增殖率,突出了 SFRP2 的刺激作用和 SFRP3 的抑制作用。在这里,我们试图确定 GC 激动剂对 SFRPs 表达的影响及其对毛囊生长的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92e3/10545675/f7b60dfe4624/41598_2023_43688_Fig1_HTML.jpg

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