Evidence for the involvement of TGF-β and PDGF in the regulation of prolyl 4-hydroxylase and lysyloxidase in cultured rat lung fibroblasts

Koslowski, Roland; Seidel, D.; Kuhlisch, Eberhard; Knoch, Klaus-Peter

doi:10.1078/0940-2993-00323

Cited by 19 publications

(12 citation statements)

References 29 publications

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“…PDGF increases the expression of fibronectin, MMP-1, thrombospondin, prolyl 4-hydroxylase, and LOX in the lung and kidney (30,31). The same genes were increased in bone by continuous PTH in this and other studies (15), suggesting continuous PTH executes its fibrotic action, at least in part, through activating the PDGF signaling pathway.…”

Section: Discussionmentioning

confidence: 54%

Osteitis Fibrosa Is Mediated by Platelet-Derived Growth Factor-A Via a Phosphoinositide 3-Kinase-Dependent Signaling Pathway in a Rat Model for Chronic Hyperparathyroidism

et al. 2008

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Abnormal secretion of PTH by the parathyroid glands contributes to a variety of common skeletal disorders. Prior studies implicate platelet-derived growth factor-A (PDGF-A) as an important mediator of selective PTH actions on bone. The present studies used targeted gene profiling and small-molecule antagonists directed against candidate gene products to elucidate the roles of specific PTH-regulated genes and signaling pathways. A group of 29 genes in rats continuously infused with PTH and cotreated with the PDGF receptor antagonist trapidil were differentially expressed compared with PTH treatment alone. Several of the identified genes were functionally clustered as regulators of fibroblast differentiation and extracellular matrix modeling, including the matrix cross-linking enzyme lysyl oxidase (LOX). Treatment with beta-aminopropionitrile, an irreversible inhibitor of LOX activity, dramatically reduced diffuse mineralization but had no effect on PTH-induced fibrosis. In contrast, the receptor tyrosine kinase inhibitor Gleevec and the phosphoinositide 3-kinase inhibitor wortmannin each reduced bone marrow fibrosis. In summary, the present studies support the hypotheses that PTH-induced bone marrow fibrosis is mediated by PDGF-A via a phosphoinositide 3-kinase-dependent signaling pathway and that increased LOX gene expression plays a key role in abnormal mineralization, a hallmark of chronic hyperparathyroidism.

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Section: Discussionmentioning

confidence: 54%

Osteitis Fibrosa Is Mediated by Platelet-Derived Growth Factor-A Via a Phosphoinositide 3-Kinase-Dependent Signaling Pathway in a Rat Model for Chronic Hyperparathyroidism

et al. 2008

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“…The incorporation of collagen into the ECM of the valve cusp involves the expression and secretion of individual pro-collagen proteins into the extracellular space, the synthesis of processing enzymes such as prolyl 4-hydroxylase, lysyl hydroxylase, prolyl 3-hydroxylase, C-terminal peptidase and lysyl oxidase; the modification and aggregation of the individual subunits and the initiation of covalent cross-linking in collagens [19,20]. The measurement of collagen present in the medium represents the secretion stage of this process.…”

Section: Discussionmentioning

confidence: 99%

Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch

Johnson

Batten

et al. 2006

Cardiovascular Research

164

111

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“…Transforming growth factor-b1 (TGFb1) up-regulated both LysOX mRNA and protein levels in human embryonic lung fibroblasts (Roy et al 1996;Choung et al 1998), human gingival fibroblasts (Hong et al 1999), and myofibroblast-like cells in the flexor reticulum of carpal tunnel syndrome patients (Bose et al 2000). In rodents TGF-b1 induced up-regulation of LysOX mRNA and protein levels was found in neonatal rat lung fibroblasts (Boak et al 1994;Koslowski et al 2003), the osteoblastic mouse cell line MC3T3-E1 (Shibanuma et al 1993;Feres-Filho et al 1995). TGF-b regulation of LysOX activity was also reported in rat aortic smooth muscle cells (Shanley et al 1997;Gacheru et al 1997).…”

Section: Transcriptional Regulation Of Lysoxmentioning

confidence: 96%

Lysyl oxidase: a potential target for cancer therapy

2010

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Lysyl oxidases (LysOX; EC 1.4.3.13, protein-lysine 6-oxidases) are extracellular copper enzymes that catalyze the cross-linking of collagens or elastin in the extracellular matrix (ECM), thereby regulating the tensile strength of tissues. Recent implication of LysOX in cancer, wound healing, cell motility, chemotaxis, and differentiation reflects its remarkable functional diversity and also in the central nervous system pathologies. However, recent reports also demonstrated novel roles for LysOX, including the ability to regulate gene transcription, motility/migration, and cell adhesion. These diverse functions have led researchers to hypothesize that LysOX may have multiple roles affecting both extra- and intracellular cell function(s). Both down and up-regulation of LysOX in tumor tissues and cancer cell lines have been described, suggesting a dual role for LysOX as a tumor suppressor, as well as a metastasis promoter gene. In this review we explain in detail the role of lysyl oxidase in tumor progression and metastasis.

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Evidence for the involvement of TGF-β and PDGF in the regulation of prolyl 4-hydroxylase and lysyloxidase in cultured rat lung fibroblasts

Cited by 19 publications

References 29 publications

Osteitis Fibrosa Is Mediated by Platelet-Derived Growth Factor-A Via a Phosphoinositide 3-Kinase-Dependent Signaling Pathway in a Rat Model for Chronic Hyperparathyroidism

Osteitis Fibrosa Is Mediated by Platelet-Derived Growth Factor-A Via a Phosphoinositide 3-Kinase-Dependent Signaling Pathway in a Rat Model for Chronic Hyperparathyroidism

Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch

Lysyl oxidase: a potential target for cancer therapy

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