SHH Protein, Human (C24II)

Sonic Hedgehog (SHH) Protein is a secreted glycoprotein of the Hedgehog family whose transcription is regulated by a long-range regulatory mechanism involving multiple enhancers. The N-terminus of SHH Protein contains a cysteine-rich domain with glycosylation sites and a cholesterol-binding domain at the C-terminus, which can form an N-terminal active fragment (N-SHH) by self-cleavage. In the endoplasmic reticulum, ShhC is degraded, leaving behind the lipidated ShhNp that is essential for developmental patterning. SHH Protein is extensively modified by cleavage and post-translational modifications, and its release from producer cells can also be regulated by interactions with Dispatched, Scube2, and heparan sulfate proteoglycans.
SHH signaling is involved in embryonic development (including lung) and patterning during development. As a ligand of the classic Hedgehog signaling pathway, SHH Protein binds to the transmembrane receptor Frizzled (such as Frizzled-1) and the co-receptor LRP6, activates Smoothened (Smo) and inhibits GSK-3β, relieves β-catenin degradation and causes its nuclear translocation, and activates anti-apoptotic genes such as FOXM1. At the same time, SHH Protein can promote NO release by phosphorylating eNOS through the PI3K/Akt pathway and shorten the action potential duration (APD) of cardiomyocytes. The biological activities of SHH Protein include promoting the maturation of sweat gland cells in three-dimensional culture (upregulating markers such as CK19) and myocardial protection in the pig ischemia-reperfusion model (reducing infarct volume and inhibiting arrhythmias). It is mainly used in the research of tissue engineering (sweat gland regeneration), ischemic diseases (such as myocardial infarction), prostate cancer and other diseases^{[1][2][3][4][5]}.