Hedgehog signaling pathway (primary ligand: Sonic hedgehog protein) (HH pathway (for pathway); SHH (for Sonic hedgehog protein))

The Hedgehog signaling pathway is a highly conserved intercellular signaling cascade critical for embryonic development, morphogenesis, and adult tissue homeostasis. The canonical pathway is triggered when secreted Hedgehog ligands (primarily Sonic hedgehog in mammals) bind to the Patched (PTCH) receptor, relieving its inhibition on Smoothened (SMO), which then activates GLI transcription factors to regulate target gene expression. In endothelial cells, Hedgehog signaling is essential for proper vascular development and angiogenesis, regulating expression of factors such as VEGF and CYR61 and influencing endothelial cell proliferation, migration, and arterial-venous identity. Aberrant Hedgehog signaling has been implicated in a variety of pathologies, including cancers (where the pathway promotes tumor vascularization and growth), tissue fibrosis, developmental disorders, and diabetic wound healing. As such, multiple Hedgehog pathway components, especially SMO, are targeted by clinically approved drugs, with ongoing research exploring new inhibitors and therapeutic strategies[1][2][3][4][5].

Other names

Sonic hedgehog (SHH)Indian hedgehog (IHH)Desert hedgehog (DHH)Patched receptor (PTCH)Smoothened receptor (SMO)GLI1Hedgehog pathway

Inhibition of Smoothened: blocks downstream Hedgehog signaling, reducing activation of GLI transcription factors and thereby impeding tumor growth and aberrant angiogenesis\nStimulation of Hedgehog: increases angiogenesis, cell proliferation, and tissue regeneration under some conditions