Authors: Katsuyuki Fujinami | Nanami Tominaga | Katsuaki Dan | Toshiko Kagawa | Ikuo Kawamura
Source: Medical Research Archives (article, 2025-01-01)
Field: Materials Science — Materials Chemistry

Polyoxometalates-mediated regulation of melanin biosynthesis and macrophage function in skin homeostasis The skin is a complex multilayered organ that performs essential functions such as barrier protection, immune and chemical defense, sensory perception, and metabolic regulation. Physiological homeostasis can be influenced by psychosocial stress, aging, and immune cell activity in the tissue microenvironment. Among resident cells, fibroblasts synthesize extracellular matrix components, while melanocytes generate melanin, the pigment responsible for freckles and age spots. Cutaneous homeostasis is continuously maintained through immune surveillance. Macrophages play a crucial role by phagocytosing foreign materials and senescent cells, as well as producing nitric oxide, cytokines, and chemokines that regulate inflammation. Recent studies have suggested that skin macrophages recognize aged cells via stabilin-1 (STAB1), remove them through phagocytosis, and release fibroblast growth factor-2 (FGF2) to signal neighboring stem cells, thus promoting regeneration. Polyoxometalates (PMs) exhibit a remarkable diversity of structural motifs, comprising clusters formed through hydrogen bonding between basic units. These basic units are composed of transition metal atoms coordinated by six or eight oxygen atoms. These compounds exhibit antibacterial and antiviral properties, and have attracted attention for their potential use in dermatological and anti-aging applications. Three PMs—VB1 (VOSO₄), VB2 (K₁₁H[(VO)₃ (SbW₉O₃₃)₂]·27H₂O), and VB3 (Na₂[SbW₉O₃₄]·19H₂O)—have been reported to demonstrate antioxidant and anti-aging effects in skin fibroblasts and mesenchymal stem cells, mediated in part by enhanced cystine uptake and, possibly, the subsequent enhancement of glutathione synthesis. In this study, we employed a three-dimensional human epidermal model comprising keratinocytes and melanocytes to demonstrate that VBs influence melanin synthesis and penetrate the epidermal layer. The potential effects of VBs on macrophage-mediated regulation of senescence and tissue regeneration were also investigated using the human monocytic U937 cell line. Taken together, these results indicate that VBs inhibit melanin synthesis by suppressing tyrosinase activity. Furthermore, VBs can penetrate the epidermal layer and act on macrophages localized in the dermis, where they upregulate STAB1 and FGF2 expression. These findings suggest that VBs modulate macrophage functions through enhanced recognition of senescent cells and regenerative signaling. Indeed, VBs were experimentally confirmed to upregulate STAB1 and FGF2 expression in macrophages using the U937 cell line. It is likely that they act as bioactive compounds that modulate pigment metabolism and immune homeostasis, as well as contribute to skin renewal and anti-aging-related processes. Homeostasis ; Immune system ; Melanin ; Chemokine ; Macrophage ; Fibroblast ; Reactive oxygen species ; Melanocyte ; Extracellular matrix ; Nitric oxide Polyoxometalates: Synthesis and Applications ; Vanadium and Halogenation Chemistry ; Metalloenzymes and iron-sulfur proteins