Sonic hedgehog protein (SHH) (SHH)

The Sonic hedgehog (Shh) signaling pathway is a fundamental regulator of hair follicle morphogenesis and the hair growth cycle (Chiang et al., 1999; PubMed: 10551986). In the skin, Shh is primarily produced by the hair follicle epithelium and acts on the underlying mesenchymal cells to promote the transition from the resting (telogen) phase to the active growth (anagen) phase (St-Jacques et al., 1998; PubMed: 9808634). The pathway involves the binding of the Shh ligand to its receptor, Patched-1 (PTCH1), which relieves inhibition of the G protein-coupled receptor-like protein Smoothened (SMO). This relief leads to the activation of GLI transcription factors, which regulate genes involved in cell proliferation and differentiation (Oro & Higgins, 2003; PubMed: 12581748). Dysregulation of this pathway is linked to various conditions; overactivation is a hallmark of basal cell carcinoma, while its suppression is associated with hair loss (Sekulic et al., 2012; PubMed: 22670903). Consequently, Shh pathway agonists are being explored as potential treatments for alopecia, whereas Shh inhibitors like vismodegib, used for cancer treatment, frequently list alopecia as a significant side effect (Paladini et al., 2005; PubMed: 16212561).

Other names

Sonic hedgehogSHHHHG1Sonic hedgehog signaling pathwaySonic hedgehog signaling pathway in hair follicles

The pathway is modulated by ligands (SHH) binding to Patched-1 (PTCH1), which relieves inhibition of Smoothened (SMO). SMO then triggers a signaling cascade leading to the nuclear translocation of GLI transcription factors (GLI1, GLI2, GLI3) to regulate gene expression involved in hair follicle growth and cycling (Oro & Higgins, 2003; PubMed: 12581748).