Antisense targeting of c-fos transcripts inhibits serum- and TGF-?1-stimulated PAI-1 gene expression and directed motility in renal epithelial cells

Kutz, Stacie M.; Providence, Kirwin M.; Higgins, Paul J.

doi:10.1002/1097-0169(200103)48:3<163::aid-cm1006>3.0.co;2-c

Cited by 14 publications

(8 citation statements)

References 61 publications

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“…Transcriptional reprogramming initiated by members of the transforming growth factor-β (TGF-β)/activin superfamily (e.g., TGF-β1) regulates cell growth, motility, matrix remodeling and pericellular proteolytic activity [1][2][3][4][5][6]. The resulting changes in cellular "plasticity" often reflect acquisition of a migratory or invasive phenotype with transcriptional activation of both serine proteases (e.g., urokinase plasminogen activator [uPA]) and matrix metalloproteinases (MMPs) as well as their specific inhibitors (PAI-1, TIMPs) [3,4,[7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…The resulting changes in cellular "plasticity" often reflect acquisition of a migratory or invasive phenotype with transcriptional activation of both serine proteases (e.g., urokinase plasminogen activator [uPA]) and matrix metalloproteinases (MMPs) as well as their specific inhibitors (PAI-1, TIMPs) [3,4,[7][8][9][10][11][12][13]. PAI-1 in particular is among the most highly upregulated genes in the TGF-β1 transcriptome (e.g., [9]; reviewed in [8,14]) and modulates the extent/ locale of stromal proteolysis, integrin-/uPA receptor (uPAR)-mediated adhesion and motile signaling through the low density lipoprotein receptor-related protein (LRP) [1,2,[14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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TGF-β1-induced PAI-1 expression is E box/USF-dependent and requires EGFR signaling

Kutz

Higgins

Samarakoon

et al. 2006

Experimental Cell Research

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TGF-β1-induced PAI-1 expression is E box/USF-dependent and requires EGFR signaling

Kutz

Higgins

Samarakoon

et al. 2006

Experimental Cell Research

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“…These results are not unanticipated, as c-fos is the prototype of the so-called early immediate genes whose expression after mitogen stimulation is immediately induced, quickly returns to baseline, and is followed by a second wave of induction. 34,35 The c-fos gene product is a major component of Cell lysates were immunoblotted with specific antibodies against ␣-SMA and GAPDH, respectively. E: Schematic diagram shows the signal pathways mediating the mitogenic action of tPA in renal interstitial fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

tPA Is a Potent Mitogen for Renal Interstitial Fibroblasts

Hao

Shen

Hou

et al. 2010

The American Journal of Pathology

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Proliferation and expansion of interstitial fibroblasts are predominant features of progressive chronic kidney diseases. However, how interstitial fibroblast proliferation is controlled remains ambiguous. Here we show that tissue-type plasminogen activator (tPA) is a potent mitogen that promotes interstitial fibroblast proliferation through a cascade of signaling events. In vitro, tPA promoted cell proliferation of rat kidney fibroblasts (NRK-49F), as assessed by cell counting, cell proliferation assay, and bromodeoxyuridine labeling. tPA also accelerated NRK-49F cell cycle progression. Fibroblast proliferation induced by tPA was associated with an increased expression of numerous proliferation-related genes, including c-fos, c-myc, proliferating cell nuclear antigen, and cyclin D1. The mitogenic effect of tPA was independent of its protease activity, but required LDL receptor-related protein 1. Interestingly, inhibition of ␤1 integrin signaling prevented tPA-mediated fibroblast proliferation. tPA rapidly induced tyrosine phosphorylation of focal adhesion kinase (FAK), which led to activation of its downstream mitogen-activated protein kinase signaling. Blockade of FAK, but not integrin-linked kinase, abolished the tPA-triggered extracellular signalregulated protein kinase 1/2 activation, proliferationrelated gene induction, and fibroblast proliferation. In vivo, proliferation of interstitial myofibroblasts in tPA null mice was attenuated after obstructive injury, compared with the wild-type controls. These studies illustrate that tPA is a potent mitogen that promotes renal interstitial fibroblast proliferation through LDL receptor-related protein 1-mediated ␤1 integrin and FAK signaling.

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“…It was highly expressed in the kidney and most commonly associated with pathological changes of the kidney. TGF-β 1 became the treatment target recently [9][10][11][12][13][14]. In this study, we have examined the protein and mRNA expression of the TGF-β 1 gene in 3 groups by IHC and real-time RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

“…However, methylation is a reversible modification of DNA participating in epigenetic regulation of gene expression. If we were going to start looking for 'epigenetic signatures' associated with various diseases on the basis of genomewide chromatin profiling or merely concentrate on specific loci or groups of genes, knowledge of where CpG methylation occurs within the genome (or epigenome) will be invaluable [14]. In addition to advancing basic research, the methylation research has immediate applications for diagnostics, and as epigenetic alterations are potentially reversible, it would has potential applications for therapeutics as well.…”

Section: Discussionmentioning

confidence: 99%

TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

Miao

Wang²,

Hu³

et al. 2010

Folia Histochem Cytobiol.

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Abstract:The aim of the study was the explain the mechanism related to therapeutic effects of Uremic Clearance Granules (Niaoduqing Keli in Chinese) on adenine-induced Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected and randomly divided in to 3 groups: Normal Control Group (NCG)consisted of 10 rats, Chronic Renal Failure Pathological Control Group (PCG) 10 rats, and Uremic Clearance Granules Treatment Group (UCG) 10 rats. Each rat in PCG and UCG was fed with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks. After fed with adenine, each rat in UCG was administered orally with 2 ml solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42 and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were determined. The methylation of TGF-β 1 promoter was tested by methylation-specific PCR. TGF-β 1 mRNA and protein expression in rat renal cortex were analyzed by real-time RT-PCR and Immunohistochemistry. (1) Experimented on model of Chronic Renal Failure in rats, the preparation was proved to be able to reduce serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05), improve renal function. (2) The expression of TGF-β 1 in mRNA and protein level were down-regulated. (3) TGF-β 1 promoter was demethylated at some loci in PCG, and was recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic Renal Failure Wistar rat's kidney function was recovered. The recovery may be result of the remethylation of TGF-β 1 promoter and then lead to TGF-β 1 be transcripted and translated normally. The experimental study explain the molecular mechanism by which Uremic Clearance Granules treat Chronic Renal Failure.

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Antisense targeting of c-fos transcripts inhibits serum- and TGF-?1-stimulated PAI-1 gene expression and directed motility in renal epithelial cells

Cited by 14 publications

References 61 publications

TGF-β1-induced PAI-1 expression is E box/USF-dependent and requires EGFR signaling

TGF-β1-induced PAI-1 expression is E box/USF-dependent and requires EGFR signaling

tPA Is a Potent Mitogen for Renal Interstitial Fibroblasts

TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

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