TRANSFORMING-GROWTH-FACTOR-BETA-1 AND ITS LATENT FORM BINDING-PROTEIN-1 ASSOCIATE WITH ELASTIC FIBERS IN HUMAN DERMIS - ACCUMULATION IN ACTINIC DAMAGE AND ABSENCE IN ANETODERMA

Latent transforming growth factor-beta 1 (TGF-beta 1) and its binding protein-1 (LTBP-1) are components of the extracellular matrix microfib rils 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 connectiv e tissue matrix of the human dermis. Prominent LTBP-1 specific fibrill ar 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 pse udoxanthoma elasticum, TGF-beta 1 had a staining pattern similar to th at of LTBP-1 in solar elastosis and solar keratosis. No staining for L TBP-1 or TGF-beta 1 was found in dermis devoid of elastic fibres, as i n anetoderma. LTBP-1 is released from the extracellular matrix of cult ured 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 p retreatment commonly used in immunohistochemistry. These results indic ate that LTBP-1 is a component of the elastin-associated microfibrils of the interstitial connective tissue matrix of human skin, Furthermor e, 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 laten t 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.