Differential Expression of Hedgehog and Snail in Cutaneous Fibrosing Disorders: Implications for Targeted Inhibition
Division of Rheumatology, Department of Medicine
Dermatology | Pathology | Skin and Connective Tissue Diseases
OBJECTIVES: To examine Hedgehog signaling in cutaneous fibrosing disorders for which effective approved therapies are lacking, expand our knowledge of pathophysiology, and explore the rationale for targeted inhibition.
METHODS: Stain intensity and percentage of cells staining for Sonic hedgehog (Shh), Indian hedgehog (Ihh), Patched (Ptch), glycogen synthase kinase 3 beta (GSK3-beta), beta-catenin, and Snail were evaluated in human skin biopsy specimens of keloid, hypertrophic scar (Hscar), scleroderma, nephrogenic systemic fibrosis (NSF), scar, and normal skin using a tissue microarray.
RESULTS: Ihh, but not Shh, was detected in a significantly larger proportion of cells for all case types. Ptch, GSK3-beta, and beta-catenin showed a gradient of expression: highest in NSF and keloid; moderate in normal skin, scar, and Hscar; and lowest in scleroderma. Snail expression was binary: low in normal skin but high in all fibrosing conditions studied.
CONCLUSIONS: Differential overexpression of Hedgehog and Snail in cutaneous fibrosing disorders demonstrates a role for targeted inhibition. Ptch, GSK3-beta, and beta-catenin can help differentiate scleroderma from NSF in histologically subtle cases. Differences in expression between keloid and hypertrophic scar support the concept that they are pathophysiologically distinct disorders. Our findings implicate Snail as a target for the prevention of fibrogenesis or fibrosis progression and may offer a means to assess response to therapy.
Dermatopathology, Fibrosis, Hedgehog, Scleroderma, Snail
DOI of Published Version
Am J Clin Pathol. 2016 Dec;146(6):709-717. doi: 10.1093/ajcp/aqw192. Link to article on publisher's site
American journal of clinical pathology
Goyal, Amrita; Linskey, Katy R.; Kay, Jonathan; Duncan, Lyn M.; and Nazarian, Rosalynn M., "Differential Expression of Hedgehog and Snail in Cutaneous Fibrosing Disorders: Implications for Targeted Inhibition" (2016). University of Massachusetts Medical School Faculty Publications. 1227.