Enhanced expression of transforming growth factor-beta type I and type II receptors in wound granulation tissue and hypertrophic scar

Am J Pathol. 1998 Feb;152(2):485-93.

Abstract

In the present study we have analyzed and compared, by immunohistochemistry and in situ hybridization, the expression pattern of the R4/ALK5 transforming growth factor (TGF)-beta type I receptor (RI) and the TGF-beta type II receptor (RII) in normal human skin, in wounded skin at various stages during the transition of wound granulation tissue to scar, and in long-persisting post-burn hypertrophic scars. In normal human skin, expression of RI and RII was clearly visible in the epidermis, in epidermal appendages, and in vascular cells, although only a small number of dermal fibroblasts revealed detectable levels of TGF-beta receptor expression. In contrast, granulation tissue fibroblasts showed strong expression of both TGF-beta receptor types, although in normal-healing excisional wounds their density decreased during granulation tissue remodeling. However, in post-burn hypertrophic scars, RI- and RII-overexpressing fibroblasts were found in high densities up to 20 months after injury. From these findings we suggest that the repair process of deep wounds involves the transformation of a subset of fibroblastic cells toward an increased TGF-beta responsiveness and a transient accumulation of these cells at the wound site. In addition, our study provides evidence that excessive scarring is associated with a failure to eliminate TGF-beta receptor-overexpressing fibroblasts during granulation tissue remodeling, which leads to a persistent autocrine, positive feedback loop that results in over-production of matrix proteins and subsequent fibrosis.

MeSH terms

  • Actins / metabolism
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cicatrix, Hypertrophic / metabolism*
  • Female
  • Granulation Tissue / metabolism*
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Muscle, Smooth / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Reference Values
  • Wound Healing / physiology*

Substances

  • Actins
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta