Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10803022 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2008 | 15 Pages |
Abstract
Latent transforming growth factor-β binding proteins are a family of extracellular matrix proteins comprising four isoforms (LTBP-1, -2, -3, -4) with different structures, tissue expression patterns and affinity for TGF-β. So far, respective knockout models have highlighted some essential functions for LTBP-2, LTBP-3 and LTBP-4, while the physiological significance of LTBP-1 is only superficially known. Here we report for the first time the generation and characterization of a mouse model lacking both the long and short LTBP-1 isoform. Surprisingly, respective mice are viable and fertile. However, detailed X-ray analysis of the skull revealed a modified facial profile. In addition, the gene disruption induces a reduced biological activity of TGF-β that became evident in an experimental model of hepatic fibrogenesis in which the LTBP-1 knockout animals were less prone to hepatic fibrogenesis. Furthermore, comparative cDNA microarray gene expression profiling of cultured hepatic stellate cells confirmed that respective nulls were less receptive to cellular activation and transdifferentiation into myofibroblasts. Therefore, we conclude that LTBP-1 has essential functions in the control of TGF-β activation.
Keywords
HBSSLatent transforming growth factor-β binding proteinTGF-βLTBP-1LTBPLAPFCSECMHRPGAPDHα-SMAHSCEGFα-smooth muscle actintransforming growth factor-βHank's buffered saline solutionMicroarrayfetal calf serumStellate cellsEmbryonic stem cellsHepatic stellate cell(s)epidermal growth factorLiver fibrogenesisExtracellular matrixhorse radish peroxidaselatency associated proteinglyceraldehyde-3-phosphate dehydrogenase
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Authors
Falko Drews, Sebastian Knöbel, Markus Moser, Kai G. Muhlack, Simone Mohren, Christian Stoll, Andreas Bosio, Axel M. Gressner, Ralf Weiskirchen,