Glucocorticoid regulation of insulin-like growth factor-binding protein-3.

Villafuerte, Betty C.; Koop, B L; Pao, Ching-I; Phillips, Lawrence S.

doi:10.1210/endo.136.5.7536659

Cited by 34 publications

(21 citation statements)

References 37 publications

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“…In accordance with our results, dexamethasone and cortisol consistently decrease IGFBP-5 levels in bone cells (Okazaki et al 1994) and fibroblasts (Conover et al 1995). In contrast to our results, however, IGFBP-3 was found to be downregulated by dexamethasone in bone cells (Okazaki et al 1994), hepatic cells (Villafuerte et al 1995) and articular chondrocytes (DiBattista et al 1996). Regulation of IGFBP-3 by glucocorticoids was also studied in vivo.…”

Section: Figuresupporting

confidence: 90%

Differential regulation of IGF-binding proteins in rabbit costal chondrocytes by IGF-I and dexamethasone

Koedam

Hoogerbrugge²,

Buul-Offers³

2000

Journal of Endocrinology

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Cartilage is a primary target tissue for the IGFs. The mitogenic activity of these peptides is regulated by a family of high-affinity IGF-binding proteins (IGFBP-1 to -6). We characterized the IGFBPs produced by cultured chondrocytes derived from rib cartilage of prepubertal rabbits. Culture medium, which had been conditioned by these cells for 48 h showed bands of 22 kDa, 24 kDa and a 31/32 kDa doublet by Western ligand blotting with [ 125

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Section: Figuresupporting

confidence: 90%

Differential regulation of IGF-binding proteins in rabbit costal chondrocytes by IGF-I and dexamethasone

Koedam

Hoogerbrugge²,

Buul-Offers³

2000

Journal of Endocrinology

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“…Our previous studies demonstrated that the Kupffer and sinusoidal endothelial cells of the liver are the locus of both high basal expression of the IGFBP-3 gene and transcriptional regulation of IGFBP-3 by insulin (27,28). In this investigation, we used transient transfection of these nonparenchymal cells to identify sequences within the Ϫ1150 to Ϫ1124 bp region of the IGFBP promoter that are required for the response to insulin.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous investigations showed that IGFBP-3 mRNA is an abundant transcript in the liver and is secreted by the Kupffer and sinusoidal endothelial cells (27). Through sequential collagenase/Pronase treatment, we were able to isolate nonparenchymal cells that express IGFBP-3 and maintain the phagocytic function of Kupffer cells, and we have used this cultured cell model to study the mechanisms involved in the hormonal regulation of IGFBP-3.…”

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confidence: 99%

Identification of an Insulin-responsive Element in the Rat Insulin-like Growth Factor-binding Protein-3 Gene

Villafuerte

Zhao

Herington

et al. 1997

Journal of Biological Chemistry

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The hepatic expression and serum levels of insulinlike growth factor-binding protein-3 (IGFBP-3) are decreased in insulin-dependent and insulin-resistant diabetes. Insulin increases hepatic IGFBP-3 expression by enhancing gene transcription. This report identifies sequences within the IGFBP-3 promoter that are necessary and sufficient for the response to insulin in hepatic nonparenchymal cells. By transient transfection, we mapped the insulin response element to the ؊1150 to ؊1124 base pair (bp) region of the rat IGFBP-3 promoter. Three tandem repeats of the ؊1150 to ؊1117 bp region conferred insulin responses in a heterologous promoter. Gel shift analyses revealed a 3-fold increase in DNAprotein complex formation with nuclear extracts obtained from insulin-stimulated nonparenchymal cells compared with cells incubated without insulin and revealed 3-4-fold decrease in complex formation with nuclear extracts obtained from the livers of streptozotocindiabetic rats compared with control rats. Mutational analysis of this 34-bp region showed a core sequence of 10 bp (؊1148 to ؊1139) that is critical for interaction with insulin-induced trans-acting factors. Southwestern blotting revealed a ϳ90-kDa protein that was increased 2-3-fold by the addition of insulin. Thus, we have identified cis-acting DNA sequences that are responsible for regulation of IGFBP-3 transcription by insulin and essential for binding of insulin-responsive nuclear factors.

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“…Several studies have indicated that these proteins are produced in different hepatic cell populations. Rat hepatocytes have been shown to secrete IGFBP-1, IGFBP-2, and IGFBP-4 (Bö ni-Schnetzler et al, 1990;Menuelle et al, 1995;Villafuerte et al, 1991), whereas IGFBP-3 expression was only found in Kupffer cells, endothelial cells, and hepatic stellate cells (Scharf et al, 1995(Scharf et al, , 1996(Scharf et al, , 1998aVillafuerte et al, 1994Villafuerte et al, , 1995. IGF-I is mainly released from hepatocytes (Kachra et al, 1991;Scharf et al, 1998a;Scott et al, 1985aScott et al, , 1985b.…”

mentioning

confidence: 99%

Analysis of the IGF Axis in Preneoplastic Hepatic Foci and Hepatocellular Neoplasms Developing after Low-Number Pancreatic Islet Transplantation into the Livers of Streptozotocin Diabetic Rats

Scharf¹,

Ramadori²,

Dombrowski

2000

Laboratory Investigation

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SUMMARY:Preneoplastic hepatic foci have been demonstrated in liver acini, which drain the blood from intraportally transplanted pancreatic islets in streptozotocin-induced diabetic rats with mild persisting diabetes. In long-term studies of this animal model, hepatocellular adenomas and carcinomas (HCC) developed after a sequence of characteristic preneoplastic hepatic foci. In this experimental model, the local hyperinsulinism is thought to have a causative role. Because insulin and the insulin-like growth factor (IGF) axis are closely linked, an altered gene expression of the IGF axis components is likely. Therefore, preneoplastic hepatic foci and HCC were studied for the expression of IGF axis components. Glycogen-storing "early" preneoplastic hepatic foci were detectable several days after pancreatic islet transplantation. Northern blot analysis, in-situ hybridization, and immunohistochemical studies of these "early" lesions demonstrated increased expressions of IGF-I and IGF binding protein-4 (IGFBP-4) in altered parenchymal cells, and a decreased expression of IGFBP-1. IGF-II was not detected in these preneoplastic foci. HCC arising in this model had decreased expressions of IGF-I and IGFBP-4 but IGFBP-1 expression was not significantly altered. Some HCC showed a more than 100-fold overexpression of IGF-II, whereas other tumors were completely negative for IGF-II expression. Low IGF-I receptor expression was detected in preneoplastic foci and adjacent nonaltered liver tissue. However, HCC tissue consistently showed an increased IGF-I receptor expression, rendering these tissues susceptible to the mitogenic effects of IGF. The altered gene expression in glycogen-storing preneoplastic hepatic foci, especially the up-regulation of IGF-I and IGFBP-4 with the down-regulation of IGFBP-1, resemble the insulin-dependent regulation of these components in normal rat hepatocytes. These data agree with previous studies demonstrating a correspondence of the focal character, morphology, and enzyme pattern of preneoplastic hepatic foci with insulin effects on hepatocytes. The development from preneoplastic foci to HCC may be driven by insulin itself and/or an altered IGF axis component or yet unidentified factors. (Lab Invest 2000, 80:1399-1411.

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Glucocorticoid regulation of insulin-like growth factor-binding protein-3.

Cited by 34 publications

References 37 publications

Differential regulation of IGF-binding proteins in rabbit costal chondrocytes by IGF-I and dexamethasone

Differential regulation of IGF-binding proteins in rabbit costal chondrocytes by IGF-I and dexamethasone

Identification of an Insulin-responsive Element in the Rat Insulin-like Growth Factor-binding Protein-3 Gene

Analysis of the IGF Axis in Preneoplastic Hepatic Foci and Hepatocellular Neoplasms Developing after Low-Number Pancreatic Islet Transplantation into the Livers of Streptozotocin Diabetic Rats

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