Title : Recombinant human thrombomodulin derivatives promote hair growth by enhancing dermal papilla cell survival and activating ?-catenin and VEGF signaling pathways
Abstract:
Background: Androgenetic alopecia (AGA) is the most prevalent form of hair loss in men, yet current FDA approved treatments finasteride and minoxidil exhibit limited efficacy and are often associated with undesirable side effects. This underscores the urgent need for novel therapeutic agents that address the underlying pathophysiology of AGA and improve treatment outcomes.
Objective: To investigate the potential of two recombinant human thrombomodulin (rhTM) derivatives, TMD23 and BB-101, as therapeutic candidates for AGA.
Methods: In vitro assays were performed to assess the survival of human follicle dermal papilla cells (HFDPCs) exposed to testosterone, with and without rhTM treatment. In vivo efficacy was evaluated in a 17-day mouse model of testosterone-induced alopecia. Histological analyses were conducted to examine changes in follicular density and morphology. Expression of β-catenin and VEGF proteins was analyzed by Western blotting and immunohistochemistry.
Results: Both TMD23 and BB-101 significantly improved HFDPC survival under testosterone-induced stress. In vivo, rhTM-treated mice exhibited enhanced hair regrowth and increased hair follicle size and density compared to controls. Protein analysis revealed upregulation of β-catenin and VEGF in skin tissues following rhTM administration, corroborated by immunohistochemical staining.
Conclusion: Our findings suggest that rhTM derivatives promote hair growth through follicular preservation and activation of key regenerative pathways. These molecules represent promising candidates for the development of new AGA therapies, potentially offering advantages over existing treatments.
