Basic fibroblast growth factor can mediate the early inductive events in renal development.

Perantoni, Alan O.; Dove, Lee F.; Karavanova, Irina

doi:10.1073/pnas.92.10.4696

Cited by 152 publications

(92 citation statements)

References 40 publications

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“…The FGF family of signaling molecules contributes to normal development and various physiological processes, such as neural and mesenchymal commitment/differentiation through an autocrine/paracrine loop with their receptors, indicating a prominent role for this signaling pathway in maintaining cellular plasticity (Bertrand et al, 2003;Sheng et al, 2003). In addition, accumulated evidence in various pathological conditions has indicated a dual role for FGF2 signaling in triggering different processes, such as epithelial-tomesenchymal and mesenchymal-to-epithelial transitions (Karavanova et al, 1996;Perantoni et al, 1995). Overall, these data show that interpretation of FGF2 signaling only in terms of the epithelial-to-mesenchymal transition is equivocal and does not account for the complexity of cellular plasticity processes, which are especially relevant in EOC pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

et al. 2004

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Epithelial ovarian cancer (EOC) is the gynecological disease with the highest death rate. We applied an automatic class discovery procedure based on gene expression profiling to stages III-IV tumors to search for molecular signatures associated with the biological properties and progression of EOC. Using a complementary DNA microarray containing 4451 cancer-related, sequence-verified features, we identified a subset of EOC characterized by the expression of numerous genes related to the extracellular matrix (ECM) and its remodeling, along with elements of the fibroblast growth factor 2 (FGF2) signaling pathway. A total of 10 genes were validated by quantitative real-time polymerase chain reaction, and coexpression of FGF2 and fibroblast growth factor receptor 4 in tumor cells was revealed by immunohistochemistry, confirming the reliability of gene expression by cDNA microarray. Since the functional relationships among these genes clearly suggested involvement of the identified molecular signature in processes related to epithelial-stromal interactions and/or epithelial-mesenchymal cellular plasticity, we applied supervised learning analysis on ovarian-derived cell lines showing distinct cellular phenotypes in culture. This procedure enabled construction of a gene classifier able to discriminate mesenchymal-like from epithelial-like cells. Genes overexpressed in mesenchymal-like cells proved to match the FGF2 signaling and ECM molecular signature, as identified by unsupervised class discovery on advanced tumor samples. In vitro functional analysis of the cell plasticity classifier was carried out using two isogenic and immortalized cell lines derived from ovarian surface epithelium and displaying mesenchymal and epithelial morphology, respectively. The results indicated the autocrine, but not intracrine stimulation of mesenchymal conversion and cohort/scatter migration of cells by FGF2, suggesting a central role for FGF2 signaling in the maintenance of cellular plasticity of ovary-derived cells throughout the carcinogenesis process. These findings raise mechanistic hypotheses on EOC pathogenesis and progression that might provide a rational underpinning for new therapeutic modalities.

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Section: Discussionmentioning

confidence: 99%

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

et al. 2004

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“…It could also be that Midkine's actions in the fetal kidney depend on additional growth factors as reported in studies showing a positive interaction between FGF2 and Midkine in craniofacial development. 19,39 Multiple FGF family members have been implicated in renal development including FGF8, FGF7 and FGF28, 14,40,41 and one or more of these factors might modulate the mitogenic effects of Midkine shown in our studies. Since the ureteric bud has long been recognized to play an essential role in the survival of the metanephric mesenchyme 5,6,29,42 and is the source of many secreted survival and mitogenic factors, 7,9 we analyzed whether the anti-apoptotic effects of Midkine depend on the presence of the ureteric bud.…”

Section: Discussionmentioning

confidence: 95%

Midkine Promotes Selective Expansion of the Nephrogenic Mesenchyme during Kidney Organogenesis

Qiu¹,

Hyink²,

Gans³

et al. 2004

Organogenesis

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During kidney development, the growth and development of the stromal and nephrogenic mesenchyme cell populations and the ureteric bud epithelium is tightly coupled through intricate reciprocal signaling mechanisms between these three tissue compartments. Midkine, a target gene activated by retinoid signaling in the metanephros, encodes a secreted polypeptide with mitogenic and anti-apoptotic activities in a wide variety of cell types. Using immmunohistochemical methods we demonstrated that Midkine is found in the uninduced mesenchyme at the earliest stages of metanephric kidney development and only subsequently concentrated in the ureteric bud epithelium and basement membrane. The biological effects of purified recombinant Midkine were analyzed in metanephric organ culture experiments carried out in serum-free defined media. These studies revealed that Midkine selectively promoted the overgrowth of the Pax-2 and N-CAM positive nephrogenic mesenchymal cells, failed to stimulate expansion of the stromal compartment and suppressed branching morphogenesis of the ureteric bud. Midkine suppressed apoptosis and stimulated cellular proliferation of the nephrogenic mesenchymal cells, and was capable of maintaining the viability of isolated mesenchymes cultured in the absence of the ureteric bud. These results suggest that Midkine may regulate the balance of epithelial and stromal progenitor cell populations of the metanephric mesenchyme during renal organogenesis.

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“…This implied involvement of FGF1 and FGF7 in developmental changes between E10.5 and E13.5, despite no detected changes in levels of transcripts for these factors. Both FGF1 and FGF2 have previously been impli- cated in metanephric development (Perantoni et al, 1995;Barasch et al, 1997;Qiao et al, 2001;Zhao et al, 2004). While the FGFs are secreted via a mechanism distinct from the use of an ER signal peptide (Prudovsky et al, 2003) and hence would not have been included in the soluble/secreted class using our prediction tools, these transcripts were actually not outliers themselves, highlighting the need for parallel analyses of signalling pathways.…”

Section: Ingenuity Pathway Analysismentioning

confidence: 96%

Definition and spatial annotation of the dynamic secretome during early kidney development

et al. 2006

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The term "secretome" has been defined as a set of secreted proteins (Grimmond et al.[2003] Genome Res 13:1350 -1359). The term "secreted protein" encompasses all proteins exported from the cell including growth factors, extracellular proteinases, morphogens, and extracellular matrix molecules. Defining the genes encoding secreted proteins that change in expression during organogenesis, the dynamic secretome, is likely to point to key drivers of morphogenesis. Such secreted proteins are involved in the reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM) that occur during organogenesis of the metanephros. Some key metanephric secreted proteins have been identified, but many remain to be determined. In this study, microarray expression profiling of E10.5, E11.5, and E13.5 kidney and consensus bioinformatic analysis were used to define a dynamic secretome of early metanephric development. In situ hybridisation was used to confirm microarray results and clarify spatial expression patterns for these genes. Forty-one secreted factors were dynamically expressed between the E10.5 and E13.5 timeframe profiled, and 25 of these factors had not previously been implicated in kidney development. A text-based anatomical ontology was used to spatially annotate the expression pattern of these genes in cultured metanephric explants.

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Basic fibroblast growth factor can mediate the early inductive events in renal development.

Cited by 152 publications

References 40 publications

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

Midkine Promotes Selective Expansion of the Nephrogenic Mesenchyme during Kidney Organogenesis

Definition and spatial annotation of the dynamic secretome during early kidney development

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