The Androgen-THY1 Axis Mediates Sexual Dimorphism in Dermal Adipogenesis and Fibrosis

    July 2025 in “ Journal of Investigative Dermatology ”
    X. Zhang, X. Zhang, Xiaoli Ji, J. Li, Lina Sun, Xinyuan Zhang
    TLDR Androgens reduce THY1 in skin cells, leading to less fat, more fibrosis, and worse healing in males.
    This study investigates the sexual dimorphism in dermal white adipose tissue (dWAT) and its underlying mechanisms. It was found that male dWAT volume decreases rapidly by 2 months of age, while female dWAT is more resistant to age-related changes. Single-cell RNA sequencing revealed that dermal fibroblasts (dFBs) are the most sex-biased cell type, with females expressing higher levels of Thy1 and males showing increased expression of fibrotic genes. Androgen receptor (AR) signaling in dFBs was shown to contribute to these differences by downregulating THY1 expression. Thy1 knockout mice exhibited thinner fat layers and more collagen deposition, indicating increased fibrosis. In a wound-induced skin fibrosis model, Thy1 deletion hindered dWAT regeneration and increased ECM accumulation, while inhibiting AR signaling restored THY1 expression and improved skin regeneration in males. The findings suggest that androgen-driven loss of THY1 in dFBs inhibits adipogenesis, promotes fibrosis, and impairs regeneration, enhancing the understanding of skin sexual dimorphism.
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