Ciliary Mechanism of Regulating Hedgehog and Wnt/β-Catenin Signaling Modulates Ultraviolet B Irradiation-Induced Photodamage in HaCaT Cells

: Skin undergoes photoaging, typically characterized by UV-damage lesions with matrix degradation and inflammatory changes. This process involves Hedgehog (Hh) signaling and the canonical Wnt pathway. Recently, primary cilia-microtubule-based organelles-have been implicated in the transduction of Hh and Wnt signaling. However, their role in photoaging remained unclear. In this study, we have shown that UVB causes both upregulation of MMPs and proinflammatory cytokines, as well as cilia formation in HaCaT cells, and that these changes can be attenuated by ciliogenesis inhibitor HPI-4 and anti-inflammatory PD98059 treatment. These cellular processes involved downregulation of transcriptional activity of components of Hh signaling, Gli1 and Gli2, as well as the turnover of p-β-catenin in canonical Wnt signaling, indicating the ciliary mechanism in photoaging. Our data demonstrate for the first time that pharmaceutical targeting of the primary cilia might have therapeutic benefits in the treatment of photoaging.