Mechanisms of microvascular wound repair II. Injury induces transformation of endothelial cells into myofibroblasts and the synthesis of matrix proteins

In Vitro Cell Dev Biol Anim. Nov-Dec 2006;42(10):314-9. doi: 10.1290/0607044.1.

Abstract

Under normal growth conditions, in vitro dermal microvascular endothelial cells (HDMEC) retain an epithelioid morphology and do not synthesize matrix proteins found increased in scar tissue. When injured by a standard scratch, cells at the wound edge and within the culture transform into spindle-shaped, myofibroblast-like cells. To determine if the transformed cells synthesize matrix proteins, expression of type I collagen and alpha smooth muscle actin (alpha-SMA) was investigated by immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Twelve hours following injury, a major upregulation in expression of alpha-SMA and type I collagen was observed both in cells proximal and distal to the wound edge. Cells with the typical morphology of myofibroblasts and displaying intracellular alpha-SMA positive fibrils were observed in HDMEC throughout the culture. In contrast, type IV collagen, a basement membrane protein, was not detected in migrating cells. Following completion of wound repair (24-36 h), type I collagen was no longer expressed and type IV collagen synthesis increased to prewound levels. Quantitative RT-PCR confirmed the changes in gene expression for both type I collagen and alpha-SMA at each time point during repair. These results demonstrate that normal skin microvascular endothelial cells retain an ability to transform into myofibroblast-like cells when injured and to synthesize matrix proteins not expressed in noninjured cells. The synthesis of matrix proteins by injured endothelial cells suggests a direct role for the endothelium in the pathology of scar formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis
  • Actins / genetics
  • Actins / metabolism
  • Blood Vessels / physiology*
  • Cell Line, Transformed
  • Cell Size
  • Collagen Type I / biosynthesis
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type IV / biosynthesis
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism
  • Dermis / blood supply
  • Dermis / cytology
  • Endothelial Cells / cytology*
  • Endothelial Cells / pathology*
  • Extracellular Matrix Proteins / biosynthesis*
  • Fibroblasts / cytology*
  • Gene Expression Regulation
  • Humans
  • Time Factors
  • Wound Healing*

Substances

  • Actins
  • Collagen Type I
  • Collagen Type IV
  • Extracellular Matrix Proteins