Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression

Tissue stiffening is a hallmark of fibrotic disorders but has traditionally been regarded as an outcome of fibrosis, not a contributing factor to pathogenesis. In this study, we show that fibrosis induced by bleomycin injury in the murine lung locally increases median tissue stiffness sixfold relative to normal lung parenchyma. Across this pathophysiological stiffness range, cultured lung fibroblasts transition from a surprisingly quiescent state to progressive increases in proliferation and matrix synthesis, accompanied by coordinated decreases in matrix proteolytic gene expression. Increasing matrix stiffness strongly suppresses fibroblast expression of COX-2 (cyclooxygenase-2) and synthesis of prostaglandin…

• NS
  National Science Foundation

  Award: 0335765
• AT
  American Thoracic Society
• CF
  Coalition for Pulmonary Fibrosis
• PF
  Pulmonary Fibrosis Foundation
• HU
  Harvard University
• NI
  National Institutes of Health

  Award: ECS-0335765
• FO
  Faculty of Arts and Sciences