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Abstract
Androgenetic alopecia (AGA) is the most common progressive form of hair loss, occurring in more than half of men aged > 50 years. Hair follicle (HF) miniaturization is a feature of AGA, and dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Previous studies have revealed that adhesion signals are important factors in AGA development. Zyxin (ZYX) is an actin-interacting protein that is essential for cell adhesion and migration. The aim of this research was to investigate the expression and potential role of ZYX in AGA. Real-time polymerase chain reaction (RT-PCR) analysis revealed that ZYX expression was elevated in the affected frontal HF of individuals with AGA compared to unaffected occipital HF. Moreover, increased ZYX expression was also observed within DP using immunofluorescence staining. Our in vivo results revealed that ZYX knockout mice showed enhanced hair growth and anagen entry compared to wild-type mice. Reducing ZYX expression in ex vivo cultured HFs by siRNA resulted in the enhanced hair shaft production, delayed hair follicle catagen entry, increased the proliferation of dermal papilla cells (DPCs), and upregulated expression of stem cell-related proteins. These results were further validated in cultured DPCs in vitro. To further reveal the mechanism by which ZYX contributes to AGA, RNA-seq analysis was conducted to identify gene signatures upon ZYX siRNA treatment in cultured hair follicles. Multiple pathways, including focal adhesion and HIF-1 signaling pathways, were found to be involved. Collectively, we discovered the elevated expression of ZYX in the affected frontal hair follicles of AGA patients and revealed the effects of ZYX downregulation on in vivo mice, ex vivo hair follicles, and in vitro DPC. These findings suggest that ZYX plays important roles in the pathogenesis of AGA and stem cell properties of DPC and may potentially be used as a therapeutic target in AGA.
Highlights
Androgenic alopecia (AGA) is a common chronic and progressive alopecia disease that can occur in both men and women
We discovered that ZYX expression increased Androgenetic alopecia (AGA) Hair follicle (HF) and dermal papillae (DP), which suggests that ZYX play a stimulatory role in AGA
Ex vivo cultured HFs and in vitro dermal papilla cells (DPCs), we found that reduced ZYX expression enhances hair shaft production, delays HF catagen entry, and enhances DPC proliferation and inductivity
Summary
Androgenic alopecia (AGA) is a common chronic and progressive alopecia disease that can occur in both men and women. The incidence of AGA is higher in Caucasians than in other populations (Otberg et al, 2007). The main manifestations of AGA in males include frontotemporal hairline recession, whereas females mainly exhibit diffuse hair loss. The hair cycle mainly consists of anagen, catagen, and telogen phases. The majority of hair is in the anagen phase and lasts the longest. In individuals with AGA, the anagen phase is shorter, while the telogen phase is longer. This change leads to the transformation of hair from terminal to vellus and hair follicle miniaturization in individuals with AGA (Lolli et al, 2017). DPC can induce hair regeneration and maintain hair in the growth stage through its stem cell characteristics (Yang and Cotsarelis, 2010)
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