The cutaneous microfibrillar apparatus contains latent transforming growth factor-beta binding protein-1 (LTBP-1) and is a repository for latent TGF-beta1.
The transforming growth factors-beta1 and beta2 (TGF-beta) stimulate synthesis of extracellular matrix proteins in vitro and appear upregulated in fibrotic conditions, in scar formation, and in wound healing. The extracellular matrix in turn might also act as a scavenger or repository for TGF-beta. We therefore studied the in situ distribution of latent TGF binding protein-1 (LTBP-1) and latent TGF-beta1 on extracellular matrix elements of normal human skin and skin regenerating from cultured keratinocyte autografts. We localized both LTBP-1 and latent TGF-beta1 to fibrillin-containing (elastic) microfibrils. Both LTBP-1 and latent TGF-beta1 were already present during the earliest stages of the de novo formation of the microfibrillar apparatus, i.e., on fusiform, randomly oriented microfibrils that later coalesced to form the typical candelabra-like structures in the papillary dermis. We show herewith that LTBP-1 exerts a dual role as a component of fibrillin-microfibrils of the skin and in targeting latent TGF-beta1 to the cutaneous microfibrillar apparatus. Thus, this major connective tissue structure does not only serve as a force bearing element and scaffold for elastin deposition in the dermis, but also as an important repository for latent TGF-beta in the skin.
Department of Dermatology, University of Münster, Germany.
M
M
Raghunath
C
C
Unsöld
U
U
Kubitscheck
L
L
Bruckner-Tuderman
R
R
Peters
M
M
Meuli
D000328:Adult; D000906:Antibodies; D002352:Carrier Proteins / Q000032:analysis* / Q000276:immunology; D002648:Child; D003429:Cross Reactions / Q000276:immunology; D046508:Culture Techniques; D004548:Elasticity; D016326:Extracellular Matrix Proteins / Q000276:immunology; D000071837:Fibrillins; D005341:Fibrinolysin / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins / Q000276:immunology; D012038:Regeneration / Q000187:drug effects; D012867:Skin / Q000737:chemistry*; D012879:Skin Physiological Phenomena; D016212:Transforming Growth Factor beta
D000906:Antibodies; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D000071837:Fibrillins; D047908:Intracellular Signaling Peptides and Proteins; C509032:LTBP1 protein, human; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; D005341:Fibrinolysin