Stimulation of Collagen Formation by Insulin and Insulin-Like Growth Factor I in Cultures of Human Lung Fibroblasts*

Goldstein, Ronald H.; Poliks, Christine F.; Pilch, Paul F.; Smith, Barbara D.; Fine, Alan

doi:10.1210/endo-124-2-964

Cited by 215 publications

(148 citation statements)

References 27 publications

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“…IGF-I was shown to stimulate collagen in human lung fibroblasts in vitro (24). IGF-I is secreted by fetal rat lung fibroblasts and stimulates cell multiplication in an autocrine or paracrine fashion (25).…”

Section: Pulmonary Fibr Oblast Elastin 25mentioning

confidence: 99%

IGF-I Stimulates Tropoelastin Synthesis in Neonatal Rat Pulmonary Fibroblasts

Noguchi

Nelson

1991

Pediatr Res

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ABSTRACT. We have examined the effect of IGF-I on tropoelastin (TE) synthesis in cultured rat neonatal pulmonary fibroblasts, because this growth factor has been shown to stimulate TE synthesis in vascular smooth muscle cells. IGF-I stimulated TE and total protein synthesis in a dose-dependent manner even when cells were cultured in the medium supplemented with 0.5% FCS. The maximal stimulation was at IGF-I concentration 500 ng/mL and was an increase of 86 f 14 and 35 f 5% for TE and estimated total protein synthesis, respectively. There was a corresponding 95 f 20% increase in the TE mRNA/fi-actin mRNA ratio assessed by densitometry of the Northern blot analysis. At this low concentration of FCS, however, there was neither TE stimulation by dexamethasone alone nor in combination with IGF-I. We conclude that IGF-I stimulation of TE synthesis may occur in cells other than vascular smooth muscle cells and that there is no additive stimulation by glucocorticoids. (Pediatr Res 30: 248-251, 1991) Abbreviations RPF, rat pulmonary fibroblasts TE, tropoelastin DEX, dexamethasone An extracellular protein component, elastin, may play an important role in the formation of the terminal airsac/alveolus during perinatal lung morphogenesis in various animals and in humans (1-8).The pro-form protein, TE, is a soluble protein of approximately 72 000 to 75 000 molecular weight (9, lo), and the regulation of synthesis is poorly understood, partly because regulatory elements of the gene have not been fully defined (1 1). We have previously demonstrated that cultured RPF are elastogenic in early passaged cells and that TE expression is stimulated by DEX (12). To further understand the humoral factors that could stimulate TE synthesis in the developing lung, we have examined IGF-I in the present study. IGF-I has been shown to stimulate TE expression in vascular smooth muscle tissue and cells (13,14), but this effect on other cell types including RPF has not been reported. We found that IGF-I stimulates TE synthesis in the neonatal RPF in a dose-dependent manner. MATERIALS AND METHODSapolis, IN). The project was approved by the Animal Care Committee of St. Louis University. Postnatal d 1 was counted as the birth date, and RPF were isolated as described before (12). Selection of the ages and response to DEX stimulation was dependent on our previous finding that TE expression is maximum at 7 d (12). Pups from two or three litters were combined and were used for extraction of total RNA and isolation of pulmonary fibroblasts by the differential adhesion method (1 5). The cells were passaged once and maintained in RPMI 1640 supplemented with 10% FCS until just before confluency and then in RPMI 1640 with 0.5% FCS to minimize the IGF-I effects of the FCS (14). At this FCS concentration, the results were more consistent than with 0.1 % FCS. Twelve h after the medium switch, cells were treated with increasing concentrations of IGF-I for another 48 h, harvested by 0.25% trypsin and 0.0 1 % EDTA treatment, and processed for extraction of tot...

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Section: Pulmonary Fibr Oblast Elastin 25mentioning

confidence: 99%

IGF-I Stimulates Tropoelastin Synthesis in Neonatal Rat Pulmonary Fibroblasts

Noguchi

Nelson

1991

Pediatr Res

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“…Collagen biosynthesis is also known to be regulated by IGF-I receptor. IGF-I, acting predominantly through the IGF-I receptor [8]. The expression of the receptor was increased in MCF-7 cancer cell lines treated with 20 μM Pt1-Pt4 and 20 μM of cisplatin for 24 h (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…Collagen biosynthesis is regulated by the signal mediated by activated β 1 -integrin receptors [8]. The expression of the receptor in MCF-7 cell lines was measured by western immunoblot.…”

Section: Resultsmentioning

confidence: 99%

“…Collagen biosynthesis is regulated by the signal mediated by activated β 1 -integrin receptors and IGF receptor [8]. Stimulated β 1 -integrin receptors induce autophosphorylation of non-receptor focal adhesion kinase pp125 FAK (FAK) [9], which is then capable of interacting with adaptor-proteins, such as Grb2, through Src and Shc proteins.…”

Section: Introductionmentioning

confidence: 99%

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Novel dinuclear platinum(II) complexes targets NFkappaB signaling pathway to induce apoptosis and inhibit metabolism of MCF-7 breast cancer cells.

Popławska

Bielawska²,

Surażyński³

et al. 2010

Folia Histochem Cytobiol.

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Four novel dinuclear platinum(II) complexes of formula [Pt 2 L 4 (berenil) 2 ]Cl 4 (Pt1-Pt4) where L is piperazine (Pt1), 4-picoline (Pt2), 3-picoline (Pt3) or isopropylamine (Pt4) were compared to cisplatin in respect to collagen biosynthesis, β 1 -integrin receptor, IGF-I receptor, phosphorylated MAP-kinases (ERK 1 /ERK 2 and p38), phosphorylated Akt kinase expression and appearance of apoptosis in MCF-7 breast cancer cells. It was found that Pt1-Pt4 were more active inhibitor of collagen biosynthesis than cisplatin. The expression of IGF-I and β 1 integrin receptor, as well as phosphorylated MAPK, (ERK 1 and ERK 2 and p38) was significantly increased in cells incubated for 24 h with 20 μM Pt1-Pt4 compared to the control, not treated cells. The phenomenon was related to the increase expresion of NFκB by Pt1-Pt4 as shown by Western immunoblot analysis. Experiments made with annexin V-FITC and detection of apoptosis by a fluorescent microscopy assay revealed that novel dinuclear platinum(II) complexes (Pt1-Pt4) inhibited the proliferation of MCF-7 breast cancer cells by increasing the number of apoptotic and necrotic cells.

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“…8 IGF-1 stimulates proliferation of fibroblasts where it may act synergistically with other fibrogenic growth factors, and is also a potent inducer of collagen synthesis. 9,10 Increased IGF-1 messenger RNA (mRNA) has been detected in lung tissues following the induction of bleomycin-induced pulmonary fibrosis in mice. 7 TGF-b1 is also a potent chemoattractant of fibroblasts and is consistently found to be upregulated at sites of fibrogenesis, including pulmonary fibrosis.…”

Section: Cox-2mentioning

confidence: 99%

Fatal pulmonary fibrosis associated with BCNU: the relative role of platelet-derived growth factor-B, insulin-like growth factor I, transforming growth factor-β1 and cyclooxygenase-2

Shen

Chiu

Chow

et al. 2004

Bone Marrow Transplant

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Summary:Pulmonary fibrosis is a severe complication associated with bis-chloronitrosourea (BCNU) therapy. However, the pathogenetic mechanism has never been well investigated. We report here a 26-year-old female with diffuse large B-cell lymphoma who died of severe pulmonary fibrosis 81 days after the administration of high-dose BCNU (600 mg/m 2 ). Thoracoscopic wedge resection of left upper lung performed 10 days before patient's death showed severe pulmonary fibrosis with prominent hyperplasia of alveolar macrophages and type II pneumocytes. We further used immunohistochemistry (IHC) to examine the relative role of platelet-derived growth factor-B (PDGF-B), insulin-like growth factor I (IGF-I), transforming growth factor-b1 (TGF-b1) and cyclooxygenase-2 (COX-2) in the pathogenesis of BCNU-related pulmonary fibrosis. Strong expressions of PDGF-B and IGF-1 on alveolar macrophages and type II pneumocytes were clearly demonstrated, but in contrast, the expressions of TGF-b1 and COX-2 were almost undetectable. In conclusion, pulmonary fibrosis can develop early and progress rapidly after the administration of high-dose BCNU. The markedly increased expression of fibrogenic factors PDGF-B and IGF-1 on hyperplastic alveolar macrophages and hyperplastic type II pneumocytes may play an important role in the fibrogenesis of this disease. These novel findings may offer specific therapeutic targets in the treatment of BCNU-associated pulmonary fibrosis.

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Stimulation of Collagen Formation by Insulin and Insulin-Like Growth Factor I in Cultures of Human Lung Fibroblasts*

Cited by 215 publications

References 27 publications

IGF-I Stimulates Tropoelastin Synthesis in Neonatal Rat Pulmonary Fibroblasts

IGF-I Stimulates Tropoelastin Synthesis in Neonatal Rat Pulmonary Fibroblasts

Novel dinuclear platinum(II) complexes targets NFkappaB signaling pathway to induce apoptosis and inhibit metabolism of MCF-7 breast cancer cells.

Fatal pulmonary fibrosis associated with BCNU: the relative role of platelet-derived growth factor-B, insulin-like growth factor I, transforming growth factor-β1 and cyclooxygenase-2

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