Transforming growth factor-β: multifunctional regulator of differentiation and development

Roberts, Anita B.; Flanders, Kathleen C.; Heine, Ursula; Jakowlew, Sonia B.; Kondaiah, Paturu; Kim, S.-J.; Sporn, Michael B.

doi:10.1098/rstb.1990.0050

Cited by 169 publications

(59 citation statements)

References 31 publications

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“…PDGF (1-8 U/ml) and IGF-II (0.5-12 ng/ml) did not stimulate migration, nor did acidic FGF (2-12 ng/ml) with or without heparin ( 1-100 pg/ml). Next affects kinetic behavioral properties ofdiverse types ofcells (30,31). Fig.…”

Section: Resultsmentioning

confidence: 99%

“…As migration ofBSC-1 cells is easily inhibited by the RGDS peptide that competes with fibronectin for its receptor, it is possible that fibronectin-integrin binding may participate in migration both in the presence and absence ofADP, as appears to be the case in other types of cells. TGF-f has been shown to modulate cellular production of matrix proteins, plasminogen activator, and plasminogen activator inhibitor (30,47), and EGF stimulates transcription of integrins in 3T3 fibroblasts (48). In rat liver epithelial cells, EGF-induced migration is associated with altered fibronectin and laminin gene expression (49), and ECM proteins appear to modulate migration (50).…”

Section: Discussionmentioning

confidence: 99%

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Adenine nucleotides stimulate migration in wounded cultures of kidney epithelial cells.

Kartha

Toback²

1992

J. Clin. Invest.

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Adenine nucleotides speed structural and functional recovery when administered after experimental renal injury in the rat and stimulate proliferation of kidney epithelial cells. As cell migration is a component of renal regeneration after acute tubular necrosis, we have used an in vitro model of wound healing to study this process. High density, quiescent monkey kidney epithelial cultures were wounded by mechanically scraping away defined regions of the monolayer to simulate the effect of cell loss after tubular necrosis and the number of cells that migrated into the denuded area was counted. Migration was independent of cell proliferation. Provision of adenosine, adenine nucleotides, or cyclic AMP increased the number of migrating cells and accelerated repair of the wound. Other purine and pyrimidine nucleotides were not effective. Arginine-glycine-aspartic acid-serine peptide, which blocks the binding of extracellular fibronectin to its cell surface receptor, completely inhibited migration in the presence or absence of ADP. Very low concentrations of epidermal growth factor (Ko.5 0.3 ng/ml) stimulated migration, whereas transforming growth factor-,82 was inhibitory (K; -0.2 ng/ml). Thus, adenosine and/or adenine nucleotides released from injured or dying renal cells, or administered exogenously, may stimulate surviving cells in the wounded nephron to migrate along the basement membrane, thereby rapidly restoring tubular structure and function. (J. Clin. Invest. 1992. 90:288-292.) Key words: acute renal failure * transforming growth factor-,@ * epidermal growth factor * heparin . extracellular matrix

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Adenine nucleotides stimulate migration in wounded cultures of kidney epithelial cells.

Kartha

Toback²

1992

J. Clin. Invest.

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“…It has been found that genistein inhibits vessel endothelial cell proliferation and in vitro angiogenesis at half maximal concentration of 5 and 150 μM, respectively, suggesting that genistein is a potent inhibitor of vascularization and cancer cell growth [104]. TGF-β is a known major factor that regulates cell proliferation [115], and TGF-β signaling is an important feature in the up-regulation of angiogenesis [116]. Genistein has been known to inhibit TGF-β signaling, and therefore inhibit angiogenesis [116].…”

Section: Effects On the Inhibition Of Angiogenesis And Metastasismentioning

confidence: 99%

Multi-targeted therapy of cancer by genistein

Banerjee¹,

Li²,

Wang³

et al. 2008

Cancer Letters

550

383

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Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers in Asian countries. Genistein, the predominant isoflavone found in soy products, has been shown to inhibit the carcinogenesis in animal models. There is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genisteinis mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. It has been shown that genistein inhibits the activation of NF-κB and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Moreover, genistein antagonizes estrogen-and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant properties, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro studies have clearly shown that genistein, one of the major soy isoflavones, is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. In this review, we attempt to provide evidence for these preventive and therapeutic effects of genistein in a succinct manner highlighting comprehensive state-of-the-art knowledge regarding its multi-targeted biological and molecular effects in cancer cells.

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“…TGF-␤ regulates cell growth, cell differentiation, immune and inflammatory responses, extracellular matrix production, and apoptosis (22,23). TGF-␤ signaling is mediated by transmembrane serine/threonine kinase receptors that phosphorylate the receptor-regulated Smads, Smad2 and Smad3.…”

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confidence: 99%

Identification of Glucocorticoid Receptor Domains Involved in Transrepression of Transforming Growth Factor-β Action

Wang

Gelehrter

2003

Journal of Biological Chemistry

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The transforming growth factor-␤ (TGF-␤) and glucocorticoid signaling pathways interact both positively and negatively in regulating a variety of physiological and pathologic processes. We previously reported that liganded glucocorticoid receptor (GR) repressed TGF-␤ induction of human plasminogen activator inhibitor-1 gene transcription by directly targeting the transcriptional activation function of Smad3. To identify the domain(s) in the glucocorticoid receptor involved in this repression, we have examined the ability of various GR truncation, deletion, and substitution mutants to repress TGF-␤ transactivation in Hep3B human hepatoma cells that lack functional endogenous GR. Partial deletions in the ligand-binding domain (LBD), including the 2 and c regions, greatly reduced or eliminated GR repression, whereas deletion of the N-terminal AF1 ( 1) domain and substitution mutations in the DNA-binding domain had little or no effect. Liganded androgen receptor repressed TGF-␤ transactivation, whereas mineralocorticoid receptor did not, and studies with rat GRmineralocorticoid receptor chimeras confirmed that the GR C-terminal domains were required for repression. RU486, a strong antagonist of transactivation by GR, partially reversed repression by wild type GR. Co-immunoprecipitation experiments in Hep3B cells indicated that physical interaction between GR and Smad3 is necessary but not sufficient for repression. Physical interaction required activation of Smad3 by TGF-␤ but not dexamethasone binding to GR. Glutathione S-transferase pull-down assays demonstrated that several regions of the LBD could mediate GR-Smad3 physical interaction. We conclude that the LBD of GR, but not the DNAbinding domain or the N-terminal activation domain, is required for GR-mediated transrepression of TGF-␤ transactivation.

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Transforming growth factor-β: multifunctional regulator of differentiation and development

Cited by 169 publications

References 31 publications

Adenine nucleotides stimulate migration in wounded cultures of kidney epithelial cells.

Adenine nucleotides stimulate migration in wounded cultures of kidney epithelial cells.

Multi-targeted therapy of cancer by genistein

Identification of Glucocorticoid Receptor Domains Involved in Transrepression of Transforming Growth Factor-β Action

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