Transforming growht factor β1 and its latent form binding protein‐1 associate with elastic fibres in human dermis: accumulation in actinic damage and absence in anetoderma

Summary Latent transforming growth factor‐β1 (TGF‐β1) 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‐β1 and LTBP‐1 and compred their distribution iwth 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‐β1 had a staining pattern similar to that of LTBP‐1 in solar elastosis and solar kertosis. No staining for LTBP‐1 or TGF‐β1 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. Analyogously, the immunoreactivity for LTBP‐1 and TGF‐β1 were also lost form 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‐β1 is likely to associate with the extracellular matrix of human dermis via LTBP‐1. The release of latent TGF‐β1 from the matrix, as a consequence of proteolytic cleavage of LTBP‐1, is a plausible extracellular mechanism for the regulation of TGF‐β1 activation.