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.
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.
Karonen
T
T
Department of Dermatology, University of Helsinki, Finland.
Jeskanen
L
L
Keski-Oja
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001284:Atrophy; D015415:Biomarkers / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D004547:Elastic Tissue / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008875:Middle Aged; D009506:Nevus / Q000378:metabolism; D010787:Photosensitivity Disorders / Q000378:metabolism*; D011561:Pseudoxanthoma Elasticum / Q000378:metabolism; D012867:Skin / Q000737:chemistry*; D012871:Skin Diseases / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis*
D015415:Biomarkers; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C509032:LTBP1 protein, human; D053779:Latent TGF-beta Binding Proteins; D016212:Transforming Growth Factor beta