Fibronectin regulates growth factor signaling and cell differentiation in primary lens cells

Judy K. VanSlyke, Bruce A. Boswell, Linda Musil

Research output: Contribution to journalArticle

Abstract

Lens epithelial cells are bound to the lens extracellular matrix capsule, of which laminin is a major component. After cataract surgery, surviving lens epithelial cells are exposed to increased levels of fibronectin, and so we addressed whether fibronectin influences lens cell fate, using DCDML cells as a serum-free primary lens epithelial cell culture system. We found that culturing DCDMLs with plasma-derived fibronectin upregulated canonical TGFβ signaling relative to cells plated on laminin. Fibronectin-exposed cultures also showed increased TGFβ signaling-dependent differentiation into the two cell types responsible for posterior capsule opacification after cataract surgery, namely myofibroblasts and lens fiber cells. Increased TGFβ activity could be identified in the conditioned medium recovered from cells grown on fibronectin. Other experiments showed that plating DCDMLs on fibronectin overcomes the need for BMP in fibroblast growth factor (FGF)-induced lens fiber cell differentiation, a requirement that is restored when endogenous TGFβ signaling is inhibited. These results demonstrate how the TGFβ-fibronectin axis can profoundly affect lens cell fate. This axis represents a novel target for prevention of late-onset posterior capsule opacification, a common but currently intractable complication of cataract surgery.

Original languageEnglish (US)
Article numberjcs217240
JournalJournal of Cell Science
Volume131
Issue number22
DOIs
StatePublished - Nov 1 2018

Fingerprint

Fibronectins
Lenses
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Cataract
Capsule Opacification
Epithelial Cells
Laminin
Myofibroblasts
Fibroblast Growth Factors
Conditioned Culture Medium
Capsules
Extracellular Matrix
Cell Culture Techniques
Serum

Keywords

  • Cataract
  • Epithelial-mesenchymal transition
  • Fibrosis
  • Lens
  • TGFβ

ASJC Scopus subject areas

  • Cell Biology

Cite this

Fibronectin regulates growth factor signaling and cell differentiation in primary lens cells. / VanSlyke, Judy K.; Boswell, Bruce A.; Musil, Linda.

In: Journal of Cell Science, Vol. 131, No. 22, jcs217240, 01.11.2018.

Research output: Contribution to journalArticle

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