Raghunath M, Unsöld C, Kubitscheck U, Bruckner-Tuderman L, Peters R, Meuli M
Department of Dermatology, University of Münster, Germany.
J Invest Dermatol. 1998 Oct;111(4):559-64. doi: 10.1046/j.1523-1747.1998.00339.x.
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.
转化生长因子-β1和-β2（TGF-β）在体外刺激细胞外基质蛋白的合成，并且在纤维化状态、瘢痕形成和伤口愈合中似乎上调。反过来，细胞外基质也可能作为TGF-β的清除剂或储存库。因此，我们研究了潜伏性TGF结合蛋白-1（LTBP-1）和潜伏性TGF-β1在正常人皮肤以及培养的角质形成细胞自体移植再生皮肤的细胞外基质成分上的原位分布。我们将LTBP-1和潜伏性TGF-β1都定位到含原纤蛋白（弹性）的微原纤维上。在微原纤维装置从头形成的最早阶段，即梭形、随机取向的微原纤维上就已经存在LTBP-1和潜伏性TGF-β1，这些微原纤维后来合并形成乳头真皮中典型的烛台样结构。我们在此证明，LTBP-1作为皮肤原纤蛋白-微原纤维的一个组成部分以及将潜伏性TGF-β1靶向到皮肤微原纤维装置中发挥双重作用。因此，这种主要的结缔组织结构不仅作为真皮中弹性蛋白沉积的受力元件和支架，而且作为皮肤中潜伏性TGF-β的重要储存库。
