Characterization of the Somatomedin-C/Insulin-Like Growth Factor I (SM-C/IGF-I) Receptor on Cultured Human Fibroblast Monolayers: Regulation of Receptor Concentrations by SM-C/IGF-I and Insulin*

Rosenfeld, Ron G.; Dollar, Laura A.

doi:10.1210/jcem-55-3-434

Cited by 160 publications

(62 citation statements)

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“…Twelve of 23 GDIgG preparations tested in that earlier study significantly displaced binding regardless of whether the donor manifested clinical TAO. The K d of IGF-I binding was 0.5 nM (46), consistent with that found in dermal fibroblasts (35). These earlier studies failed to identify the IGF-I binding site in fibroblasts.…”

Section: Discussionsupporting

confidence: 70%

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Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor I Receptor Pathway

Pritchard

Han

Horst

et al. 2003

The Journal of Immunology

252

243

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Graves’ disease (GD) is associated with T cell infiltration, but the mechanism for lymphocyte trafficking has remained uncertain. We reported previously that fibroblasts from patients with GD express IL-16, a CD4-specific chemoattractant, and RANTES, a C-C chemokine, in response to GD-specific IgG (GD-IgG). We unexpectedly found that these responses result from a functional interaction between GD-IgG and the insulin-like growth factor (IGF)-I receptor (IGF-IR). IGF-I and the IGF-IR-specific IGF-I analog, des(1–3), mimic the effects of GD-IgG. Neither GD-IgG nor IGF-I activates chemoattractant expression in control fibroblasts from donors without GD. Interrupting IGF-IR function with specific receptor-blocking Abs or by transiently transfecting fibroblasts with a dominant negative mutant IGF-IR completely attenuates signaling provoked by GD-IgG. Moreover, GD-IgG displaces specific 125I-labeled IGF-I binding to fibroblasts and attenuates IGF-IR detection by flow cytometry. These findings identify a novel disease mechanism involving a functional GD-IgG/IGF-IR bridge, which potentially explains T cell infiltration in GD. Interrupting this pathway may constitute a specific therapeutic strategy.

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Section: Discussionsupporting

confidence: 70%

“…These effects of disease-specific Igs can now be attributed to interactions with IGF-IR, which is widely expressed on human fibroblasts (35). Activating TSHR with TSH fails to elicit these responses.…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor I Receptor Pathway

Pritchard

Han

Horst

et al. 2003

The Journal of Immunology

252

243

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“…The finding of slightly higher levels of IGF-I binding in the liver of feed-restricted gilts is consistent with the increase in IGF-IR in some tissues in response to fasting or protein deprivation [16,35] and with data showing that IGF-I down-regulates its own receptor in vitro [29,30]. The lack of alteration of IGF-I binding in skeletal muscle and adipose tissue despite changes in plasma IGF-I concentration does not corroborate this relationship.…”

Section: Discussionsupporting

confidence: 61%

GH and IGF-I binding sites in adipose tissue, liver, skeletal muscle and ovaries of feed-restricted gilts

2000

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-The influence of feed restriction on GH and IGF-I binding was examined in the cyclic gilt. IGF-I, IGFBPs, insulin and leptin levels in plasma were also measured. Twenty-four gilts whose oestrous cycle was synchronised were used. From day 3 to day 12, (with day 0 being the first day of oestrus) feed allowance was 240% and 80% of the energy requirements for maintenance for well-fed (H) and restricted gilts (L) respectively. Six gilts in each group were treated with an antagonist of GnRH but the treatment had no effect on any reported measurements. Blood and tissue samples were collected on days 12 and 13 respectively. L gilts lost live weight whereas H gilts gained weight. Plasma IGF-I, insulin and leptin concentrations were lower in L than in H gilts whereas plasma IGFBP levels were not affected by feed restriction. The specific binding of 125 I-bGH to adipose tissue, liver, skeletal muscle and ovary membranes did not differ significantly between H and L gilts. Specific binding of 125 I-IGF-I to hepatic membranes was higher in L than in H gilts whereas it did not differ between the two groups in the other tissue membranes.

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“…Thus, the potential for growth factors and their cognate cell surface receptors to participate in this disease appears great. IGF-1R is a ubiquitous protein expressed on many cell types, including human fibroblasts (23). When ligated, the tyrosine kinase receptor initiates signaling leading to multiple cell responses, including those resulting in proliferation (24).…”

Section: Induction Of Il-16 and Rantes Expression In Ra Synovial Fibrmentioning

confidence: 99%

Synovial Fibroblasts from Patients with Rheumatoid Arthritis, Like Fibroblasts from Graves’ Disease, Express High Levels of IL-16 When Treated with Igs against Insulin-Like Growth Factor-1 Receptor

Pritchard

Tsui

Horst

et al. 2004

The Journal of Immunology

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We have reported recently that IgG from patients with Graves’ disease (GD) can induce the expression of the CD4-specific T lymphocyte chemoattractant, IL-16, and RANTES, a C-C chemokine, in their fibroblasts. This induction is mediated through the insulin-like growth factor-1 receptor (IGF-1R) pathway. We now report that Abs from individuals with active rheumatoid arthritis (RA-IgG) stimulate in their synovial fibroblasts the expression of these same cytokines. IgG from individuals without known autoimmune disease fails to elicit this chemoattractant production. Furthermore, RA-IgG fails to induce IL-16 or RANTES expression in synovial fibroblasts from donors with osteoarthritis. RA-IgG-provoked IL-16 and RANTES production also appears to involve the IGF-1R because receptor-blocking Abs prevent the response. RA fibroblasts transfected with a dominant-negative mutant IGF-1R fail to respond to RA-IgG. IGF-1 and the IGF-1R-specific analog Des(1–3) also induce cytokine production in RA fibroblasts. RA-IgG-provoked IL-16 expression is inhibited by rapamycin, a specific macrolide inhibitor of the Akt/FRAP/mammalian target of rapamycin/p70s6k pathway, and by dexamethasone. GD-IgG can also induce IL-16 in RA fibroblasts, and RA-IgG shows similar activity in GD fibroblasts. Thus, IgGs from patients with RA, like those associated with GD, activate IGF-1R, and in so doing provoke T cell chemoattraction expression in fibroblasts, suggesting a potential common pathway in the two diseases. Immune-competent cell trafficking to synovial tissue is integral to the pathogenesis of RA. Recognition of this novel RA-IgG/fibroblast interaction and its functional consequences may help identify therapeutic targets.

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Characterization of the Somatomedin-C/Insulin-Like Growth Factor I (SM-C/IGF-I) Receptor on Cultured Human Fibroblast Monolayers: Regulation of Receptor Concentrations by SM-C/IGF-I and Insulin*

Cited by 160 publications

References 0 publications

Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor I Receptor Pathway

Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor I Receptor Pathway

GH and IGF-I binding sites in adipose tissue, liver, skeletal muscle and ovaries of feed-restricted gilts

Synovial Fibroblasts from Patients with Rheumatoid Arthritis, Like Fibroblasts from Graves’ Disease, Express High Levels of IL-16 When Treated with Igs against Insulin-Like Growth Factor-1 Receptor

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