Transforming Growth Factor Beta 1 and Its Latent Form Binding protein-1 Associate With Elastic Fibres in Human Dermis: Accumulation in Actinic Damage and Absence in Anetoderma

Br J Dermatol. 1997 Jul;137(1):51-8.

Abstract

Latent transforming growth factor-beta 1 (TGF-beta 1) and its binding protein-1 (LTBP-1) are components of the extracellular matrix microfibrils of cultured human fibroblasts. Using immunohistochemistry we have studied the localization of TGF-beta 1 and LTBP-1 and compared their distribution with that of elastic fibres in the interstitial connective tissue matrix of the human dermis. Prominent LTBP-1 specific fibrillar staining co-localized with the elastic fibres in normal human skin. Co-distribution was also observed in a number of pathological states of the elastic fibres such as solar elastosis, solar keratosis and pseudoxanthoma elasticum. TGF-beta 1 had a staining pattern similar to that of LTBP-1 in solar elastosis and solar keratosis. No staining for LTBP-1 or TGF-beta 1 was found in dermis devoid of elastic fibres, as in anetoderma. LTBP-1 is released from the extracellular matrix of cultured human fibroblasts, epithelial and endothelial cells by proteases. Analogously, the immunoreactivity for LTBP-1 and TGF-beta 1 were also lost from the skin sections by elastase, and by trypsin, a protease pretreatment commonly used in immunohistochemistry. These results indicate that LTBP-1 is a component of the elastin-associated microfibrils of the interstitial connective tissue matrix of human skin. Furthermore, the small latent form of TGF-beta 1 is likely to associate with the extracellular matrix of human dermis via LTBP-1. The release of latent TGF-beta 1 from the matrix, as a consequence of proteolytic cleavage of LTBP-1, is a plausible extracellular mechanism for the regulation of TGF-beta 1 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Atrophy
  • Biomarkers / analysis
  • Carrier Proteins / analysis*
  • Child
  • Child, Preschool
  • Elastic Tissue / chemistry*
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins*
  • Latent TGF-beta Binding Proteins
  • Middle Aged
  • Nevus / metabolism
  • Photosensitivity Disorders / metabolism*
  • Pseudoxanthoma Elasticum / metabolism
  • Skin / chemistry*
  • Skin Diseases / metabolism
  • Skin Neoplasms / metabolism
  • Transforming Growth Factor beta / analysis*

Substances

  • Biomarkers
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • LTBP1 protein, human
  • Latent TGF-beta Binding Proteins
  • Transforming Growth Factor beta