Gene expression profiling reveals novel TGFβ targets in adult lung fibroblasts

Renzoni, Elisabetta A.; Abraham, David; Howat, Sarah; Xu, Shiwen; Sestini, Piersante; Bou‐Gharios, George; Wells, Athol U.; Veeraraghavan, Srihari; Nicholson, Andrew G.; Denton, Christopher P.; Leask, Andrew; Pearson, Jeremy D.; Black, Carol M.; Welsh, Kenneth I.; Bois, Roland M. du

doi:10.1186/1465-9921-5-24

Cited by 116 publications

(116 citation statements)

References 50 publications

(65 reference statements)

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“…The results identified several genes whose expression was induced Ն2-fold in Smad3-expressing hTERT fibroblasts at this early time point. Genes showing early up-regulation by Smad3 included EGR-1, calreticulin, RAB14, MIF, and SGK, as well as CYR61, SMAD7, and CTGF, which had been shown previously to be Smad/TGF-␤-inducible genes in fibroblasts (21,22). Of these, EGR-1 was initially chosen for further study, because this inducible zinc finger transcription factor was originally identified as an early-immediate gene induced in fibroblasts by a variety of environmental signals, and had been shown to play important roles in inflammatory and hypoxic responses, wound healing, and vascular injury.…”

Section: Identification and Validation Of Egr-1 As A Novel Smad3mentioning

confidence: 88%

The Early-Immediate Gene EGR-1 Is Induced by Transforming Growth Factor-β and Mediates Stimulation of Collagen Gene Expression

Chen

Ning

Ishida

et al. 2006

Journal of Biological Chemistry

152

156

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Section: Identification and Validation Of Egr-1 As A Novel Smad3mentioning

confidence: 88%

The Early-Immediate Gene EGR-1 Is Induced by Transforming Growth Factor-β and Mediates Stimulation of Collagen Gene Expression

Chen

Ning

Ishida

et al. 2006

Journal of Biological Chemistry

152

156

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“…NCOR2 can form a large corepressor complex and this complex associates with the thyroid and the retinoid acid receptor. NCOR2 might be the novel TGF-b responsive gene and it has been showed that exogenous TGF-b could upregulate the gene expression of NCOR2 [31]. Thus, the upregulated gene expression of NCOR2 in low oxygen tension may result from hypoxiainduced expression of TGF-b.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induces the activation of human hepatic stellate cells LX‐2 through TGF‐β signaling pathway

et al. 2006

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Hypoxia is a common environmental stress factor and is also associated with various physiological and pathological conditions such as fibrogenesis. The activation of hepatic stellate cells (HSCs) is the key event in the liver fibrogenesis. In this study, the behavior of human HSCs LX-2 in low oxygen tension (1% O 2 ) was analyzed. Upon hypoxia, the expression of HIF-1a and VEGF gene was induced. The result of Western blotting showed that the expression of a-SMA was increased by hypoxic stimulation. Furthermore, the expression of MMP-2 and TIMP-1 genes was increased. Hypoxia also elevated the protein expression of the collagen type I in LX-2 cells. The analysis of TGF-b/ Smad signaling pathway showed that hypoxia potentiated the expression of TGF-b1 and the phosphorylation status of Smad2. Gene expression profiles of LX-2 cells induced by hypoxia were obtained by using cDNA microarray technique.

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“…In lung cancer models in vitro, Spry4 has been shown to reverse the EMT phenotypes of tumor cells (42). Moreover, Spry downregulation may be required for the progression of TGFβ-induced EMT and fibrosis, because Spry2 has been shown to be downregulated in fibrotic lung fibroblasts (43)(44)(45). Consistent with this finding, Spry seems to have an inverse relationship with TGFβ, with Spry transcripts downregulated in response to TGFβ in human lens epithelial cells (46) and in mesenchymal cells (47).…”

Section: Introductionmentioning

confidence: 99%

Sprouty Is a Negative Regulator of Transforming Growth Factor β-Induced Epithelial-to-Mesenchymal Transition and Cataract

Shin

Basson

Robinson

et al. 2012

Mol Med

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Fibrosis affects an extensive range of organs and is increasingly acknowledged as a major component of many chronic disorders. It is now well accepted that the elevated expression of certain inflammatory cell-derived cytokines, especially transforming growth factor β (TGFβ), is involved in the epithelial-to-mesenchymal transition (EMT) leading to the pathogenesis of a diverse range of fibrotic diseases. In lens, aberrant TGFβ signaling has been shown to induce EMT leading to cataract formation. Sproutys (Sprys) are negative feedback regulators of receptor tyrosine kinase (RTK)-signaling pathways in many vertebrate systems, and in this study we showed that they are important in the murine lens for promoting the lens epithelial cell phenotype. Conditional deletion of Spry1 and Spry2 specifically from the lens leads to an aberrant increase in RTK-mediated extracellular signal-regulated kinase 1/2 phosphorylation and, surprisingly, elevated TGFβ-related signaling in lens epithelial cells, leading to an EMT and subsequent cataract formation. Conversely, increased Spry overexpression in lens cells can suppress not only TGFβ-induced signaling, but also the accompanying EMT and cataract formation. On the basis of these findings, we propose that a better understanding of the relationship between Spry and TGFβ signaling will not only elucidate the etiology of lens pathology, but will also lead to the development of treatments for other fibrotic-related diseases associated with TGFβ-induced EMT.

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Gene expression profiling reveals novel TGFβ targets in adult lung fibroblasts

Abstract: This study identifies several novel TGFbeta targets in lung fibroblasts, and confirms with independent methods the induction of angiotensin II receptor type 1, underlining a potential role for angiotensin II receptor 1 antagonism in the treatment of lung fibrosis.

Cited by 116 publications

References 50 publications

The Early-Immediate Gene EGR-1 Is Induced by Transforming Growth Factor-β and Mediates Stimulation of Collagen Gene Expression

The Early-Immediate Gene EGR-1 Is Induced by Transforming Growth Factor-β and Mediates Stimulation of Collagen Gene Expression

Hypoxia induces the activation of human hepatic stellate cells LX‐2 through TGF‐β signaling pathway

Sprouty Is a Negative Regulator of Transforming Growth Factor β-Induced Epithelial-to-Mesenchymal Transition and Cataract

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