2.19 - ECM Deposition and Scar Maturation

After new vessels form, fibroblasts migrate into the wound and build the new ECM. The immature repair tissue then remodels into dense mature scar.

TGF-β

oen of the most important scar/fibrosis mediators that binds and activates intracellular transcription factors called Smads

• primary functions in inflammation and repair

  • increases synthesis of collagen, fibronectin, proteoglycans to build ECM

  • inhibits collagen degradation by decreasing proteinase activity and increasing activity of tissue inhibitors of metalloproteinases (TIMPs)

• mediates fibrosis in lungs, liver, and kidneys following chronic inflammation

• anti-inflammatory cytokine that terminates inflammatory response by inhibiting WBC proliferation and activity

PDGF

stimulates migration and proliferation of fibroblasts and smooth muscle cells

• stored in platelets, endothelial cells, activated macrophages, smooth muscle cells, tumor cells

cytokines

may function as growth factors

• IL-1 and IL-13 stimulate collagen synthesis by fibroblasts and enhance fibroblastic proliferation and migration

scar remodeling and progression

with progression in repair process, vascularity/angiogenesis decreases and fibroblast proliferation decreases

• increased collagen deposition for increasing wound strength, and diminished collagen degradation

• results in wound area that transforms from primarily granulation tissue to avascular scar

  • less active fibroblasts, dense collagen and fragments of elastic tissue, and other ECM components

matrix metalloproteinases (MMPs)

zinc-dependent enzymes that break down ECM during tissue remodeling

• MMP-1,2,3 → cleave fibrillar collagen

• MM-2,9 → degrade gelatinous proteins

• MMP-3,10,11 → degrade proteoglycans, laminin, fibronectin, and amorphous collagen

• made by fibroblasts, macrophages, neutrophils, synovial cells, select epithelial cells

  • secreted as zymogens

  • inhibited by tissue inhibitors of metalloproteinases (TIMPs)