Biological insights in the pathogenesis of hypermobile Ehlers-Danlos syndrome from proteome profiling of patients' dermal myofibroblasts

Nicola Chiarelli, Nicoletta Zoppi, Marco Ritelli, Marina Venturini, Daniele Capitanio, Cecilia Gelfi, Marina Colombi

Research output: Contribution to journalArticlepeer-review


Hypermobile Ehlers-Danlos syndrome (hEDS), mainly characterized by generalized joint hypermobility and its complications, minor skin changes, and apparently segregating with an autosomal dominant pattern, is still without a known molecular basis. Hence, its diagnosis is only clinical based on a strict set of criteria defined in the revised EDS nosology. Moreover, the hEDS phenotypic spectrum is wide-ranging and comprises multiple associated signs and symptoms shared with other heritable or acquired connective tissue disorders and chronic inflammatory diseases. In this complex scenario, we previously demonstrated that hEDS patients' skin fibroblasts show phenotypic features of myofibroblasts, widespread extracellular matrix (ECM) disarray, perturbation of ECM-cell contacts, and dysregulated expression of genes involved in connective tissue architecture and related to inflammatory and pain responses. Herein, the cellular proteome of 6 hEDS dermal myofibroblasts was compared to that of 12 control fibroblasts to deepen the knowledge on mechanisms involved in the disease pathogenesis. Qualitative and quantitative differences were assessed based on top-down and bottom-up approaches and some differentially expressed proteins were proofed by biochemical analyses. Proteomics disclosed the differential expression of proteins principally implicated in cytoskeleton organization, energy metabolism and redox balance, proteostasis, and intracellular trafficking. Our findings offer a comprehensive view of dysregulated protein networks and related pathways likely associated with the hEDS pathophysiology. The present results can be regarded as a starting point for future in-depth investigations aimed to decipher the functional impact of potential bioactive molecules for the development of targeted management and therapies.

Original languageEnglish
Article number166051
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number4
Publication statusPublished - Apr 1 2021


  • Cytoskeleton remodeling and signaling
  • Hypermobile Ehlers-Danlos syndrome
  • Metabolic changes
  • Myofibroblasts
  • Proteome profiling
  • S100A4

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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