Anastellin impacts on the processing of extracellular matrix fibronectin and stimulates release of cytokines from coronary artery smooth muscle cells

Jianfei He, Jonas Hyld Steffen, Peter Waaben Thulstrup, Jannik Nedergaard Pedersen, Max B Sauerland, Daniel E Otzen, Clare L Hawkins, Pontus Gourdon, Michael J Davies, Per Hägglund

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Anastellin, a recombinant protein fragment from the first type III module of fibronectin, mimics a partially unfolded intermediate implicated in the assembly of fibronectin fibrils. Anastellin influences the structure of fibronectin and initiates in vitro fibrillation, yielding "superfibronectin", a polymer with enhanced cell-adhesive properties. This ability is absent in an anastellin double mutant, L37AY40A. Here we demonstrate that both wild-type and L37AY40A anastellin affect fibronectin processing within the extracellular matrix (ECM) of smooth muscle cells. Fibronectin fibrils are diminished in the ECM from cells treated with anastellin, but are partially rescued by supplementation with plasma fibronectin in cell media. Proteomic analyses reveal that anastellin also impacts on the processing of other ECM proteins, with increased collagen and decreased laminin detected in media from cells exposed to wild-type anastellin. Moreover, both anastellin forms stimulate release of inflammatory cytokines, including interleukin 6. At the molecular level, L37AY40A does not exhibit major perturbations of structural features relative to wild-type anastellin, though the mutant showed differences in heparin binding characteristics. These findings indicate that wild-type and L37AY40A anastellin share similar molecular features but elicit slightly different, but partially overlapping, responses in smooth muscle cells resulting in altered secretion of cytokines and proteins involved in ECM processing.

Original languageEnglish
Article number22051
JournalScientific Reports
Volume12
Issue1
Number of pages15
ISSN2045-2322
DOIs
Publication statusPublished - Dec 2022

Keywords

  • Fibronectins/metabolism
  • Cytokines/metabolism
  • Coronary Vessels/metabolism
  • Proteomics
  • Extracellular Matrix/metabolism

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