Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation.

International Journal of Molecular Sciences
Carmela FuscoMarco Castori

Abstract

Transforming growth factor β (TGF-β) superfamily signaling pathways are ubiquitous and essential for several cellular and physiological processes. The overexpression of TGF-β results in excessive fibrosis in multiple human disorders. Among them, stiff skin syndrome (SSS) is an ultrarare and untreatable condition characterized by the progressive thickening and hardening of the dermis, and acquired joint limitations. SSS is distinct in a widespread form, caused by recurrent germline variants of FBN1 encoding a key molecule of the TGF-β signaling, and a segmental form with unknown molecular basis. Here, we report a 12-year-old female with segmental SSS, affecting the right upper limb with acquired thickening of the dermis evident at the magnetic resonance imaging, and progressive limitation of the elbow and shoulder. To better explore the molecular and cellular mechanisms that drive segmental SSS, several functional studies on patient's fibroblasts were employed. We hypothesized an impairment of TGF-β signaling and, consequently, a dysregulation of the associated downstream signaling. Lesional fibroblast studies showed a higher phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2), increased levels of nuclear...Continue Reading

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Citations

Mar 27, 2021·The Australasian Journal of Dermatology·Diogo CerejeiraHenriqueta Cunha

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Methods Mentioned

BETA
biopsy
biopsies
exome sequencing
electron
nuclear translocation
PCR
electrophoresis
confocal microscopy

Software Mentioned

Image J
FATHMM
GATK
BLAT
SIFT
MetaSVM
LRT
CADD
PROVEAN
ImageJ

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