NOTCH pathway activation in infantile hemangiomas
Haihong Zhang, Ting Wei, Adam B. Johnson, Ravi W. Sun, Gresham T. Richter, Graham M. Strub
Abstract
OBJECTIVE: The objective of this study was to characterize the role of NOTCH signaling cascade activation in the angiogenic drive of infantile hemangioma (IH) tissue. METHODS: Both IH tissue and normal skin were collected from 55 surgical patients. Of these, 14 were proliferating hemangiomas, 14 were stationary, 14 were involuted, and 13 had been treated with propranolol. Protein and RNA were extracted from all tissues and subjected to Western blotting and reverse transcription-polymerase chain reaction, respectively, for components of the NOTCH signaling pathway. RESULTS: Compared with normal skin from the same patients, proliferating IHs contained higher levels of messenger RNA and protein for the majority of NOTCH receptors and ligands as well as the downstream coactivator MAML1. Expression of NOTCH receptor ligand messenger RNA and protein was significantly lower in involuting and propranolol-treated IHs. CONCLUSIONS: Perturbations in NOTCH signaling follow the natural course and treatment outcome of IHs, suggesting a critical role in their pathogenesis.