Profiling molecular targets of TGF-β1 in prostate fibroblast-to-myofibroblast transdifferentiation

Untergasser, Gerold; Gander, R.; Lilg, C.; Lepperdinger, Günter; Plas, Eugen; Berger, Peter

doi:10.1016/j.mad.2004.09.023

Cited by 162 publications

(124 citation statements)

References 39 publications

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“…However, we did not find clusters of Ecrg4+ cells in the aged brain, indicating that neighboring cells do not become senescent at one time, perhaps owing to unknown inhibitors for Ecrg4 or Ecrg4 acting in a cell-autonomous manner, as in the case of IL6 (29). Nonetheless, because other senescence-inducing secretion factors (30), including IGFBPs, IL, TGFβ, and PAI1, not only induce senescence but also cause or contribute to degenerative changes in the surrounding cells (31)(32)(33), it will be of great interest to investigate the physiological significance of Ecrg4's function. Additionally, it will be interesting to learn if its inhibition delays the processes of brain aging and if Ecrg4 contributes to differences between fetal/neonatal and adult OPCs in myelination speed and competence, as previously shown by Windrem et al (8), although Ecrg4 is unlikely to be involved in oligodendrocyte differentiation (Fig.…”

Section: -H)mentioning

confidence: 73%

Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells

Kujuro

Suzuki

Kondo

2010

Proc. Natl. Acad. Sci. U.S.A.

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Mammalian aging is thought to be partially caused by the diminished capacity of stem/precursor cells to undergo self-renewing divisions. Although many cell-cycle regulators are involved in this process, it is unknown to what extent cell senescence, first identified as irreversible growth arrest in vitro, contributes to the aging process. Here, using a serum-induced mouse oligodendrocyte precursor cell (mOPC) senescence model, we identified esophageal cancer-related gene 4 (Ecrg4) as a senescence inducer with implications for the senescence-like state of postmitotic cells in the aging brain. Although mOPCs could proliferate indefinitely when cultured using the appropriate medium (OPC medium), they became senescent in the presence of serum and maintained their senescent phenotype even when the serum was subsequently replaced by OPC medium. We show that Ecrg4 was up-regulated in the senescent OPCs, its overexpression in OPCs induced senescence by accelerating the proteasome-dependent degradation of cyclins D1 and D3, and that its knockdown by a specific short hairpin RNA prevented these phenotypes. We also show that senescent OPCs secreted Ecrg4 and that recombinant Ecrg4 induced OPC senescence in culture. Moreover, increased Ecrg4 expression was observed in the OPCs and neural precursor cells in the aged mouse brain; this was accompanied by the expression of senescence-associated β-galactosidase activity, indicating the cells' entrance into senescence. These results suggest that Ecrg4 is a factor linking neural-cell senescence and aging.cyclin D1 and D3 | neural precursor cells | oligodendrocyte precursor cells | retinoblastoma | senescence-associated β-galactosidase

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Section: -H)mentioning

confidence: 73%

Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells

Kujuro

Suzuki

Kondo

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…11 Aberrant production of growth factors occurs naturally in stroma but extensive changes in protein expression by breast cancer stroma is not accompanied by genetic alterations. 22 This implies that neoplastic epithelial cells induce the altered stromal proteome.…”

Section: Discussionmentioning

confidence: 99%

Dynamic stromal‐epithelial interactions during progression of MCF10DCIS.com xenografts

Tait

Pauley

Santner

et al. 2007

Intl Journal of Cancer

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cells form comedo type ductal carcinoma in situ in immune-deficient mice before forming invasive ductal carcinoma. As the lesions mature, both stromal and epithelial cells undergo phenotypic changes detected by immunohistochemistry. Myofibroblasts are present before the formation of carcinoma in situ and after development of invasive carcinoma. MCF10DCIS. com lesions develop a myoepithelial layer prior to exhibiting a basement membrane surrounding the ductal mass. TGFb1 is initially expressed by the epithelial cells but is expressed by stroma in invasive carcinoma. Stromal derived factor-1 is detected in epithelial cells in early carcinoma in situ but is produced in stromal cells in invasive carcinoma. The receptor CXCR4 is expressed by epithelial cells in the xenografts at all times, as is the hepatocyte growth factor receptor c-met. MCF10DCIS.com xenografts illustrate the dynamic interplay of epithelium and stroma in the development of carcinoma in situ and subsequent invasive carcinoma. Although the phenotype of the epithelial cells may be dependent upon the stroma, the malignant epithelium induces the development of the stroma necessary for progression to the invasive stage. ' 2007 Wiley-Liss, Inc.Key words: breast cancer; carcinoma in situ; MCF10DCIS.com; progression; stroma; xenograft The natural history of cancer is thought to involve multiple sequential genetic changes including mutations, loss of heterozygosity and amplification of gene copy number as well as epigenetic changes such as hypermethylation of promoter regions. In many epithelial cancers a series of abnormal histologic changes can be identified and associated with increased risk of progressing to malignant disease. It has been assumed that each stage accumulates additional genetic anomalies. The first recognized lesion with increased risk for breast cancer is hyperplasia ( a 4-fold increased risk for atypical ductal hyperplasia) but genetic anomalies are rare. ErbB2 is rarely detected in benign lesions. 1-3 However, overexpression of erbB2 is frequent in DCIS and IDC. Studies of mixed lesions, containing both in situ and invasive components, invariably report that the 2 components express erbB2 coordinately. 4-6 A similar pattern occurs for cyclin D1 expression; rare in benign hyperplastic lesions but frequent in both DCIS and IDC and expressed coordinately in both in situ and invasive components of mixed lesions. 7,8 Recent studies suggest that nearly all genetic alterations have occurred by the time of DCIS formation. Comparative genomic hybridization analysis of breast DCIS and IDC found no significant difference in the number of chromosomal abnormalities, although the frequency of a few specific changes varied in high grade versus low grade DCIS and between DCIS and concurrent IDC. 9 A more recent study confirmed that DCIS is genetically advanced. Allelic imbalance of 52 microsatellite markers of chromosomal regions commonly lost in breast cancer increased significantly between atypical ductal hyperplasia and DCIS but not between DCIS an...

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“…29 In addition, transgelin was markedly upregulated by TGF-b induced transdifferentiation of prostate fibroblasts into myofibroblasts. 30 Cellular migration and proliferation of MCs, the glomerular pericytes, are the two key features that are important for repopulation and regeneration of the glomerulus after Figure 5 Transgelin promotes mesangial cell proliferation. Double immunostaining in kidney biopsies from anti-Thy1 nephritic rats on day 5 shows that transgelin (a, green fluorescence) and the proliferation marker PCNA (b, red fluorescence) colocalizes within the glomeruli (c, orange merged fluorescence).…”

Section: Transgelin In Glomerular Regeneration C Daniel Et Almentioning

confidence: 99%

Transgelin is a marker of repopulating mesangial cells after injury and promotes their proliferation and migration

Daniel

Lüdke

Wagner

et al. 2012

Laboratory Investigation

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Mesangial cell (MC) migration is essential during glomerular repair and kidney development. The aim of the study was to identify marker/player for glomerular progenitor/reserve cells migrating into the glomerulus after MC injury and during glomerulogenesis in the rat. Experimental mesangial proliferative nephritis was induced in Sprague Dawley rats by intravenous injection of OX-7 antibody. We investigated mRNA expression profiles in isolated glomeruli from on days 0, 1, 2, 3, and 5 after induction of anti-Thy1 nephritis using Affymetrix microarray technology. Using self-organizing maps, transgelin was identified as a new marker for repopulating glomerular cells. Expression of transgelin during anti-Thy1 nephritis was investigated by northern blot, real-time PCR, western blot, and immunohistochemistry. Migration and proliferation assays using isolated MCs after transgelin knockdown by siRNA were performed to investigate the potential role of transgelin during glomerular repopulation. Transgelin mRNA was not detected in healthy glomeruli. It was strongly upregulated during the repopulation process starting on day 1, continued to be increased until day 5 and disappeared on day 7. Transgelin was specifically expressed at the edge of the migratory front during glomerular repopulation as indicated by transgelin/OX-7 double staining. Transgelin expression was similar in migrating vs non-migrating MCs in vitro. Blocking of transgelin expression by siRNA treatment resulted in inhibition of MC migration and proliferation. Transgelin was also expressed in MCs during glomerulogenesis and in biopsies from patients with IgA nephritis. In conclusion, transgelin in the kidney is upregulated in repopulating MCs in vivo and supports their migratory and proliferative repair response after injury.

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Profiling molecular targets of TGF-β1 in prostate fibroblast-to-myofibroblast transdifferentiation

Cited by 162 publications

References 39 publications

Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells

Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells

Dynamic stromal‐epithelial interactions during progression of MCF10DCIS.com xenografts

Transgelin is a marker of repopulating mesangial cells after injury and promotes their proliferation and migration

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