Disease relevance of LTBP1

• Using the baculovirus expression system, we have mapped the domain of LTBP-1 mediating covalent association with small latent TGF-beta1 [1].
• The current study was carried out to understand hormonal regulation of LTBP-1 expression in normal and SV-40 virus transformed human lung fibroblasts [2].
• TGF-beta 1 had a staining pattern similar to that of LTBP-1 in solar elastosis and solar keratosis [3].
• RESULTS: Liver biopsies from HCV patients showed positive staining for TGF-beta1-3 isoforms and LTBP, and to a lesser degree for TNF-alpha, in areas with inflammation and fibrosis [4].
• In situ expression of transforming growth factor-beta1-3, latent transforming growth factor-beta binding protein and tumor necrosis factor-alpha in liver tissue from patients with chronic hepatitis C [4].

High impact information on LTBP1

• TGF-beta 1-BP was found not to bind and inactive TGF-beta 1; its role in the latent complex is discussed [5].
• TGF-beta 1-BP purified from human platelets is considerably smaller than the fibroblast form (125-160 kd vs. 170-190 kd), suggesting that there is alternative splicing of the TGF-beta 1-BP gene or that TGF-beta 1-BP undergoes cell-specific proteolysis [5].
• Most of the sequence of fibroblast TGF-beta 1-BP is made up of cysteine-rich repeats of two different kinds; there are 16 EGF-like repeats and three repeats with a distant resemblance to EGF, but of a distinct type hitherto not found in any other protein. beta-hydroxylated asparagine residues were identified in two of the EGF-like repeats [5].
• A second pool, which contains LAP but not LTBP, is retained in the clot, but can be released by RGD peptide [6].
• LTBP was present predominantly in mononuclear cells and in the extracellular matrix around them [7].

Chemical compound and disease context of LTBP1

• Identification of transforming growth factor-beta1-binding protein overexpression in carmustine-resistant glioma cells by MRNA differential display [8].

Biological context of LTBP1

• A major difference was seen between transplanted kidneys, which exhibited clearly positive TGF-beta and LTBP1 (latent TGF-beta binding protein) immunoreactivities, and the non-transplanted kidneys [9].
• Assignment of the gene encoding the latent TGF-beta 1-binding protein (LTBP1) to human chromosome 2, region p12-->q22 [10].
• Using a panel of well-defined human x rodent somatic cell hybrid lines, LTBP1 could be assigned to chromosome 2 [10].
• The binding site was within three domains of the LTBP-1 C terminus, and in fibrillin-1 the site was defined within four domains near the N terminus [11].
• We analyzed LTBP-1 gene expression and LTBP-1 fiber appearance with respect to the emergence and distribution of cell types in differentiating EBs [12].

Anatomical context of LTBP1

• Immunoelectron microscopy confirmed localization of LTBP1 to 10- to 12-nm microfibrils and suggested an ordered aggregation of LTBP1 into these structures [13].
• LTBP1 may therefore be a candidate gene for Marfan-related connective tissue disorders in which linkage to fibrillins has been excluded [13].
• Thus, transplantation was the most important predictor for expression of TGF-beta s and LTBP1, and the largest expression increase in the allografts occurred in the interstitium, followed by the glomeruli and blood vessels [9].
• By immunostaining, fibrillar LTBP-1 was observed in those regions of the culture containing endothelial, smooth muscle, and epithelial cells [12].
• These results suggest that during differentiation of ES cells LTBP-1 facilitates endothelial cell organization via a TGF-beta-dependent mechanism [12].

Associations of LTBP1 with chemical compounds

• The cysteine required for the association between LTBP-1 and beta1-LAP was mapped to Cys33 of beta1-LAP [14].
• Latent transforming growth factor beta (TGFbeta) binding protein-1 (LTBP1) is an ECM glycoprotein that binds latent TGFbeta and regulates its availability and activity [15].
• We here report a novel form of human LTBP-1, which is longer in its NH2-terminal part (LTBP-1L) [16].
• Loss of a consensus heparin binding site by alternative splicing of latent transforming growth factor-beta binding protein-1 [17].
• Our results indicate that LTBP-1 expression is under the regulation of RA and corticoids in lung fibroblasts [2].

Physical interactions of LTBP1

• Immunoblotting of the fusion protein complexes indicated that the third 8-Cys repeat of LTBP-1 bound covalently to the LAP region of TGF-beta1 [14].
• Latent transforming growth factor beta-binding protein 1 interacts with fibrillin and is a microfibril-associated protein [11].
• In this study, we demonstrate that LTBP-1 and large latent complex are substrates for transglutaminase [18].

Co-localisations of LTBP1

• Both LTBP-1 and beta 1-LAP colocalized with fibronectin in double immunofluorescence analysis [19].

Regulatory relationships of LTBP1

• In amniotic epithelial cells, transcription of the LTBP-1S reporter gene construct was down-regulated by a distal upstream element. mRNA levels of the isoforms of LTBP-1 were stimulated in response to TGF-beta1 in WI-38 cells [20].
• However, only antibodies to the amino-terminal region of LTBP-1 block transglutaminase-dependent cross-linking of large latent complex or LTBP-1 [18].

Other interactions of LTBP1

• TGF-beta1 associates with the 3(rd) 8-Cys repeat of LTBP-1 by LAP [21].
• Immunolocalization data were consistent with the hypothesis that LTBP-1 is a fibrillin-associated protein present in certain tissues but not in others [11].
• While the domain structure of LTBP-2 is similar to that of the other LTBPs, LTBP-2 possesses unique regions that make it the largest member of the LTBP family [22].
• In addition, LTBP-1 was found in structures that were heavily labeled for fibronectin [19].
• In conclusion, TGFbeta3, TGFbeta4, TGFbetai, LTBP1 and LTBP2 may assist the process of dedifferentiation, while TGFbeta1 and beta2 might not be involved in this process [23].

Analytical, diagnostic and therapeutic context of LTBP1

• By immunohistochemistry, LTBP-1, -2, and LAP were detectable in normal and diseased livers and showed a different staining pattern for both LTBP isoforms [24].
• Metabolic labeling followed by immunoprecipitation with anti-LTBP-1 antibody revealed the synthesis of LTBP proteins [25].
• METHODS: Cultured human MFB were analyzed for TGF-beta and LTBP using reverse-transcription polymerase chain reaction (RT-PCR), sequence analysis, immunofluorescence staining, metabolic labeling, immunoprecipitation, and enzyme-linked immunosorbent assay (ELISA) [25].
• Secretion of free LTBP and LTBP integrated into the large latent TGF-beta complex was demonstrated by size-exclusion chromatography [25].
• 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 [26].

References