Expression of isoforms and splice variants of the latent transforming growth factor β binding protein (LTBP) in cultured human liver myofibroblasts

Abstract

The expression of a complete profile of hitherto known LTBP proteins by cultured human MFB suggests a role in modulating the bioactivity of TGF-beta in the diseased liver.

Expression and matrix deposition of latent transforming growth factor β binding proteins in normal and fibrotic rat liver and transdifferentiating hepatic stellate cells in culture

“…21 By confocal laser scanning microscopy, a codistribution of LTBP-1 with fibronectin and collagen type I in human MFB cultures was noticed. 19 The similar time course of the deposition of DOC-resistant LTBP-1, fibronectin, and collagen type I in our culture system suggests also for rat HSC/MFB a possible covalent extracellular assembly of these matrix components.…”

“…We additionally propose a relevant function for MFB in the extracellular activation of TGF-␤, because these cells secrete both the large, latent TGF-␤ complex 19 and the plasminogen activator inhibitor type I 49 relevant for the release of LTBP from the matrix by plasmin. As shown here, the major fraction of LTBP-1 is fixed covalently to the matrix of HSC/MFB and, thus, can be removed by proteases like plasmin.…”

“…[17][18][19] The presence of LTBP in hepatic and many extrahepatic cells suggests an important role in regulating the activity of TGF-␤. It was proposed that LTBP is crucial for the extracellular activation of TGF-␤ after covalent attachment of the large complex via LTBP to the extracellular matrix.…”

Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer

“…FSTL1 is a TGF-b-inducible gene, SPARC-related, that enhances inflammatory cytokine/chemokine expression (36) and seems to be implicated in angiogenesis and revascularization (37). Another TGF-b signaling-related protein was LTBP2, which colocalizes with fibronectin and collagen type I for ECM regulation and remodeling (38,39). LTBP2 Differentially expressed proteins were identified as preferentially expressed in smooth muscle if they were among the top five tissues with highest expression using the Bio-GPS database.…”

Genetic characteristics of the human hepatic stellate cell line LX–2

“…Human umbilical vein endothelial cells (HUVEC) were isolated from human umbilical cords by collagenase dissociation and grown medium 199 (Gibco, Life Technologies, Darmstadt, Germany) with 20% heat-inactivated fetal bovine serum (FBS) (Gibco), 100 mg/ml endothelial cell growth supplement (Sigma, Taufkirchen, Germany), and 50 U/ml heparin (Sigma). Human MFB (hMFB) were isolated as outgrowth from human liver tissues and sub-cultured for several passages as described before [19]. All experiments done with LX-2 cells were done with passages number between p5 and p7 in which these numbers refer to those after selection of an immortalized cell population [4].…”