Disease relevance of Ltbp1

• LAP has an important function in the latency of TGF-beta complex, but the role of LTBP-1 is not known in diabetic angiopathy [1].
• Induction and coexpression of latent transforming growth factor beta-binding protein-1 and fibrillin-1 in experimental glomerulonephritis [2].
• In saline-treated rats latent TGF-beta-binding protein-1 (LTBP-1) immunoreactivity was moderately elevated 3 and 6 h after ischemia, and returned to control levels after 1 day of reperfusion [3].
• Matrix-associated latent TGF-beta with LTBP may thus play an important role in the progressive process of glomerulosclerosis and interstitial fibrosis in ADR-nephropathy [4].

High impact information on Ltbp1

• CONCLUSIONS: The existence of different LTBP isoforms and splice variants in HSCs and myofibroblasts suggests multiple functions of the LTBP family in rat liver, which might not be restricted to the maintenance of TGF-beta latency [5].
• The role of the latent TGF-beta binding protein (LTBP) is unclear [6].
• Dual role for the latent transforming growth factor-beta binding protein in storage of latent TGF-beta in the extracellular matrix and as a structural matrix protein [6].
• These findings, together with the known homology of LTBP to the fibrillin family of proteins, suggest a novel function for LTBP, in addition to its role in matrix storage of latent TGF-beta, as a structural matrix protein that may play a role in bone formation [6].
• However, in situ hybridization points to a restriction of transcripts to nonparenchymal cells from fibrotic livers, whereas hepatocytes were always devoid of LTBP transcripts [7].

Biological context of Ltbp1

• In the present study, we used the reverse transcription in combination with polymerase chain reaction (RT-PCR) to investigate the precise localization of TGF-beta 1 and LTBP in the microdissected glomeruli, renal tubules and arterioles [8].
• Northern blotting analysis demonstrated that the HS diet led to the increases in cortical gene expression of TGF-beta 1, LTBP, and TGF-beta receptors, compared with the LS diet [9].

Anatomical context of Ltbp1

• Latent transforming growth factor-beta binding protein-1, a component of latent transforming growth factor-beta complex, accelerates the migration of aortic smooth muscle cells in diabetic rats through integrin-beta3 [1].
• Subcellular fractions obtained by standard differential centrifugation of rat liver homogenate were analyzed using a TGF-beta1 enzyme-linked immunosorbent assay (ELISA) and Western blotting for beta1-LAP and LTBP-1 [10].
• By confocal microscopy, a diffuse distribution of TGF-beta and LAP in the cytoplasm of PC is noticed, whereas the LTBP immunostaining predominates at plasma membranes [10].
• In HSC, stainings of colocalized TGF-beta, LAP, and LTBP are strongest in the perinuclear area, indicating synthesis and secretion via endoplasmic reticulum and Golgi, respectively [10].
• In PC, distinct intracellular granules were superimposed with TGF-beta, LAP, and LTBP stainings identified as lysosomal compartments and mitochondria by ELISA and immunoblotting of subcellular fractions [10].

Associations of Ltbp1 with chemical compounds

• Using a cell enzyme-linked immunosorbent assay (ELISA), a differential increase of partly deoxycholate (DOC)-resistant, matrix-bound LTBP-1 and -2 was measured in cultured stellate cells [7].
• Metabolic labeling of PC with [35S]-Met/Cys followed by immunoprecipitation of cell lysates with LTBP antiserum confirmed the synthesis of the high molecular mass complex of 250 kd containing LTBP with a molecular mass of 160 kd [11].
• Although 24,25 induced the expression of LTBP1 by RCs, TGF-beta1 incorporation into the matrix is not regulated by this vitamin D3 metabolite [12].
• These effects were associated with the prevention of macrophage glomerular infiltration, and the inhibition of the TGF-beta axes in foam cells as shown by the reduction in cytoplasm immunostaining for TGF-beta and LTBP-1; heparin also reduced peri-macrophagic collagen IV deposition [13].

Physical interactions of Ltbp1

• Northern blotting demonstrated the difference in the mRNA expression patterns of TGF-beta 1 and latent TGF-beta 1 binding protein (LTBP) in the cortex [14].

Regulatory relationships of Ltbp1

• LTBP was induced simultaneously with TGF-beta 1 and occurred within interstitial spaces of the myocardium [15].

Other interactions of Ltbp1

• RESULTS: Induction of glomerular LTBP-1 mRNA was detected on day 2 of disease, while mRNA for fibrillin-1 was already upregulated 1 day after induction of disease [2].
• During the transformation of HSC to myofibroblasts, LAP and LTBP become strongly colocalized with other components of the cytoskeletal network like smooth muscle--actin, desmin, and talin [10].
• When the intensity of the immunoreactivity in the injured side was compared to that of the contralateral side, significantly increasing differences were found for TGF-beta 2 (p < 0.003) and LTBP (p < 0.002) [16].
• Immunostainings of normal and fibrotic livers demonstrate intense signals for LTBP-1 and -2, preferably in parenchymal, but also nonparenchymal, cells and in fibrotic extracellular matrix [7].
• We showed that TGF-beta ligand and receptor mRNA levels did not increase during the transition to adult-type repair in fetal skin, whereas LTBP-1 and fibromodulin expression decreased [17].

Analytical, diagnostic and therapeutic context of Ltbp1

• Immunohistochemistry of fetal and adult rat bone confirmed a fibrillar staining pattern for LTBP in vivo [6].
• Real-time RT-PCR and immunohistochemical analyses for LTBP-1 and fibrillin-1 were performed [2].
• PC and HSC were isolated from rat liver by protease reperfusion and investigated for TGF-beta1,-2,-3, beta1-LAP, and LTBP-1 after cultivation using double-immunofluorescent staining, followed by high-resolution confocal microscopic analysis [10].
• Metabolic labeling followed by immunoprecipitation with LTBP antiserum confirmed the synthesis and secretion of various LTBP-related proteins [5].
• METHODS: HSCs isolated from rat liver were analyzed for LTBP and TGF-beta at various times of culture during transdifferentiation into myofibroblasts using immunocytochemical staining, metabolic labeling and immunoprecipitation, reverse-transcription polymerase chain reaction (RT-PCR), and sequencing [5].

References