9,13‐di‐<i>cis</i>‐Retinoic acid induces the production of tPA and activation of latent TGF‐β via RARα in a human liver stellate cell line, LI90

Imai, Shoko; Okuno, Masataka; Moriwaki, Hisataka; Muto, Yasutoshi; Murakami, Kazuhiro; Shudo, Koichi; Suzuki, Yasuhiro; Kojima, Soichi

doi:10.1016/s0014-5793(97)00673-x

Cited by 57 publications

(30 citation statements)

References 25 publications

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“…These factors were further shown to mediate directly the antiproliferative and proapoptotic effects of TGFb (Kansra et al, 2000;Koliopanos et al, 2002). Additionally, PDGF (platelet-derived growth factor) and plasminogen activators have been described as mediators of TGFb signaling (Battegay et al, 1990;Imai et al, 1997). We found the receptors PDGFRA and uPAR (plasminogen activator urokinase receptor) to be upregulated in ATRA exposed Wilms tumor cells.…”

Section: Smad/transforming Growth Factor-beta (Tgfb) Signalingmentioning

confidence: 67%

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

Zirn

Samans

Spangenberg³

et al. 2005

Oncogene

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Section: Smad/transforming Growth Factor-beta (Tgfb) Signalingmentioning

confidence: 67%

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

Zirn

Samans

Spangenberg³

et al. 2005

Oncogene

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“…Regulation of Tgf␤ signaling by RA has been extensively reported, but data are overall conflicting. In some cell lines, RA increases production of Tgf␤1 and its receptors, leading to growth inhibition (Batova et al, 1992;Danielpour, 1996;Falk et al, 1991;Glick et al, 1989;Imai et al, 1997;Kojima and Rifkin, 1993). RA, however, has also been reported to inhibit endogenous Tgf␤ signaling in the mesenchyme of the developing inner ear (Frenz and Liu, 2000) and palate (Yu and Xing, 2006) in mice.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Tgfβ signaling by endogenous retinoic acid is essential for primary lung bud induction

et al. 2007

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Disruption of retinoic acid (RA) signaling during early development results in severe respiratory tract abnormalities, including lung agenesis. Previous studies suggest that this might result from failure to selectively induce fibroblast growth factor 10 (Fgf10) in the prospective lung region of the foregut. Little is known about the RA-dependent pathways present in the foregut that may be crucial for lung formation. By performing global gene expression analysis of RA-deficient foreguts from a genetic [retinaldehyde dehydrogenase 2 (Raldh2)-null] and a pharmacological (BMS493-treated)mouse model, we found upregulation of a large number of Tgfβ targets. Increased Smad2 phosphorylation further suggested that Tgfβ signaling was hyperactive in these foreguts when lung agenesis was observed. RA rescue of the lung phenotype was associated with low levels of Smad2 phosphorylation and downregulation of Tgfβ targets in Raldh2-null foreguts. Interestingly, the lung defect that resulted from RA-deficiency could be reproduced in RA-sufficient foreguts by hyperactivating Tgfβ signaling with exogenous TGFβ1. Preventing activation of endogenous Tgfβsignaling with a pan-specific TGFβ-blocking antibody allowed bud formation and gene expression in the lung field of both Raldh2-null and BMS493-treated foreguts. Our data support a novel mechanism of RA-Tgfβ-Fgf10 interactions in the developing foregut, in which endogenous RA controls Tgfβ activity in the prospective lung field to allow local expression of Fgf10 and induction of lung buds.

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“…RA-activated retinoic acid receptors directly bind to the retinoic acid responsive element on the tPA gene promoter, and induce the transcriptional activation of tPA gene (Bulen et al, 1997). Plasminogen activators (uPA and tPA), and plasmin, which was proteolytically produced by the plasminogen activators, can activate the latent TGF-β and its family members (Imai et al, 1997), HGF (Mars et al, 1993), and proMMPs (Baramova et al, 1997). Thus, RAs enhance the migration, invasion and differentiation of the cells, and may act as a morphogen during the embryogenesis and the development.…”

Section: Discussionmentioning

confidence: 99%

Low-dose retinoic acid enhances in vitro invasiveness of human oral squamous-cell-carcinoma cell lines

et al. 2001

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Summary Retinoids inhibit the proliferation of several types of tumour cells, and are used for patients with several malignant tumours. In this study, we examined the effect of retinoic acids (RAs) on the invasive potentials of the oral squamous cell carcinoma (SCC) cells, BHY and HNt. BHY cells expressed all of retinoid nuclear receptors (RARα, β, γ, and RXRα) and cytoplasmic retinoic acid binding proteins (CRABP1 and CRABP2). HNt cells lacked the expression of RARβ, but expressed other nuclear receptors and CRABPs. All-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-cisRA) (10 -6 and 10 -7 M) inhibited the growth of the cells, but low-dose ATRA and 13-cisRA (10 -8 M) marginally affected the growth of the cells. Surprisingly, low-dose RAs enhanced the activity of tissue-type plasminogen activator (tPA), and activated pro-matrix metalloproteinases (proMMP2 and proMMP9). Activation of proMMP2 and proMMP9 was inhibited by aprotinin, a serineproteinase, tPA inhibitor. MATERIALS AND METHODS Cells and cell cultureBHY and HNt (Kawamata et al, 1997) cells were derived from human oral SCC tumours from patients. HT1080 cells are a human fibrosarcoma cell line purchased from Dai-Nippon Seiyaku, Osaka, Japan. All of the cells were maintained in DMEM (Life Technologies, Inc, Gaithersburg, MD) supplemented with 10% FCS (Bio-Whittaker, Walkersville, MD), 100 µg ml -1 streptomycin, and 100 U ml -1 penicillin, 0.25 µg ml -1 Amphotericin B (Life Technologies, Inc.) in a humidified atmosphere of 95% air and 5% CO 2 at 37˚C. MTT assayWe examined the effect of ATRA (Sigma, St. Louis, MO) and 13-cisRA (Sigma) on the growth of the cells by an assay in which MTT (Sigma) was used. Cells were seeded on a 96-well plate (Falcon; Becton Dickinson Labware, Lincoln Park, NJ) at 5 × 10 3 cells per well in DMEM containing 10% FCS. After 24 h, cells were washed twice with DMEM without FCS and cultured in DMEM without FCS in the presence or absence of ATRA (10 -6 , 10 -7 and 10 -8 M) or 13-cisRA (10 -6 , 10 -7 and 10 -8 M). After 3 days, the number of cells was quantitated by MTT assay (Carmichael et al, 1987). Gelatinase zymography and reverse gelatinase zymographyCells were grown to confluence in 60 mm dishes (Falcon) in the serum-supplemented medium, washed twice with serum-free DMEM, and cultured in 3 ml of serum-free DMEM in the presence or absence of ATRA (10 -8 M) or 13-cisRA (10 -8 M) for an additional 48 h. The medium was collected, clarified by centrifugation at 1800 g, and concentrated down to 0.1 ml approximately 30-fold by Centricon 10 (cut-off, Mr 10 000; Millipore Corp, Bedford, MA). We have already confirmed that the process of the protein concentration did not activate the progelatinases in the samples (Kawamata et al, 1997). The protein concentration of the samples are determined by Bio-Rad protein assay (Bio-Rad, Hercules, CA). The gels for zymorgraphy were composed of gelatin (0.1%; Sigma) and polyacrylamide (10%), and for reverse zymography, of gelatin (0.1%), polyacrylamide (12.5%) and concentrated conditioned medi...

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9,13‐di‐cis‐Retinoic acid induces the production of tPA and activation of latent TGF‐β via RARα in a human liver stellate cell line, LI90

Cited by 57 publications

References 25 publications

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

Inhibition of Tgfβ signaling by endogenous retinoic acid is essential for primary lung bud induction

Low-dose retinoic acid enhances in vitro invasiveness of human oral squamous-cell-carcinoma cell lines

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