Fibroblast growth factor (FGF) gene expression in the developing cerebellum suggests multiple roles for FGF signaling during cerebellar morphogenesis and development

Microvascular endothelial cells (ECs) represent the primary target cells during human rickettsioses and respond to infection via the activation of immediate–early signaling cascades and the resultant induction of gene expression. As small noncoding RNAs dispersed throughout the genome, microRNAs (miRNAs) regulate gene expression post-transcriptionally to govern a wide range of biological processes. Based on our recent findings demonstrating the involvement of fibroblast growth factor receptor 1 (FGFR1) in facilitating rickettsial invasion into host cells and published reports suggesting miR-424 and miR-503 as regulators of FGF2/FGFR1, we measured the expression of miR-424 and miR-503 during R. conorii infection of human dermal microvascular endothelial cells (HMECs). Our results revealed a significant decrease in miR-424 and miR-503 expression in apparent correlation with increased expression of FGF2 and FGFR1. Considering the established phenomenon of endothelial heterogeneity and pulmonary and cerebral edema as the prominent pathogenic features of rickettsial infections, and significant pathogen burden in the lungs and brain in established mouse models of disease, we next quantified miR-424 and miR-503 expression in pulmonary and cerebral microvascular ECs. Again, R. conorii infection dramatically downregulated both miRNAs in these tissue-specific ECs as early as 30 min post-infection in correlation with higher FGF2/FGFR1 expression. Changes in the expression of both miRNAs and FGF2/FGFR1 were next confirmed in a mouse model of R. conorii infection. Furthermore, miR-424 overexpression via transfection of a mimic into host ECs reduced the expression of FGF2/FGFR1 and gave a corresponding decrease in R. conorii invasion, while an inhibitor of miR-424 had the expected opposite effect. Together, these findings implicate the rickettsial manipulation of host gene expression via regulatory miRNAs to ensure efficient cellular entry as the critical requirement to establish intracellular infection.

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Adenosine Stimulates Fibroblast Growth Factor-7 Gene Expression Via Adenosine A2b Receptor Signaling in Dermal Papilla Cells

Journal of Investigative Dermatology ◽

10.1038/sj.jid.5700728 ◽

2007 ◽

Vol 127 (6) ◽

pp. 1318-1325 ◽

Cited By ~ 48

Author(s):

Masato Iino ◽

Ritsuko Ehama ◽

Yosuke Nakazawa ◽

Tokuro Iwabuchi ◽

Masashi Ogo ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Dermal Papilla ◽

Fibroblast Growth ◽

Receptor Signaling ◽

Dermal Papilla Cells ◽

Adenosine A2b Receptor ◽

A2b Receptor ◽

Adenosine A2b

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Differential induction of gene expression by basic fibroblast growth factor and neuroD in cultured retinal pigment epithelial cells

Visual Neuroscience ◽

10.1017/s0952523800171172 ◽

2000 ◽

Vol 17 (2) ◽

pp. 157-164 ◽

Cited By ~ 16

Author(s):

RUN-TAO YAN ◽

SHU-ZHEN WANG

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Basic Fibroblast Growth Factor ◽

Retinal Pigment Epithelial ◽

Retinal Pigment ◽

Fibroblast Growth ◽

Rpe Cells ◽

Pigment Epithelial ◽

Two Factors

Embryonic chick retinal pigment epithelial (RPE) cells can undergo transdifferentiation upon appropriate stimulation. For example, basic fibroblast growth factor (bFGF) induces intact RPE tissue younger than embryonic day 4.5 (E4.5) to transdifferentiate into a neural retina. NeuroD, a gene encoding a basic helix-loop–helix transcription factor, triggers de novo production of cells that resemble young photoreceptor cells morphologically and express general neuron markers (HNK-1/N-CAM and MAP2) and a photoreceptor-specific marker (visinin) from cell cultures of dissociated E6 RPE (Yan & Wang, 1998). The present study examined whether bFGF will lead to the same transdifferentiation phenomenon as neuroD when applied to dissociated, cultured E6 RPE cells, and whether interplay exists between the two factors under the culture conditions. Dissociated E6 RPE cells were cultured in the presence or absence of bFGF, and with or without the addition of retrovirus expressing neuroD. Gene expression was analyzed with immunocytochemistry and in situ hybridization. Unlike neuroD, bFGF did not induce the expression of visinin, or HNK-1/N-CAM and MAP2. However, bFGF elicited the expression of RA4 immunogenicity; yet, many of these RA4-positive cells lacked a neuronal morphology. Addition of bFGF to neuroD-expressing cultures did not alter the number of visinin-expressing cells; misexpression of neuroD in bFGF-treated cultures did not change the number of RA4-positive cells, suggesting the absence of interference or synergistic interaction between the two factors. Our data indicated that bFGF and neuroD induced the expression of different genes in cultured RPE cells.

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326 1α,25-DIHYDROXYVITAMIN D3 UP-REGULATES FIBROBLAST GROWTH FACTOR 23 GENE EXPRESSION IN A RAT OSTEOBLASTIC CELL LINE AND MOUSE CALVARIA

Journal of Investigative Medicine ◽

10.2310/6650.2005.00005.325 ◽

2005 ◽

Vol 53 (1) ◽

pp. S135.3-S135

Author(s):

O. I. Kolek ◽

E. R. Hines ◽

M. D. Jones ◽

L. LeSueur ◽

P. R. Kiela ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Cell Line ◽

Fibroblast Growth Factor 23 ◽

Osteoblastic Cell ◽

Fibroblast Growth ◽

Dihydroxyvitamin D3 ◽

Osteoblastic Cell Line ◽

Mouse Calvaria

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Defective FXR-FGF15 signaling and bile acid homeostasis in cystic fibrosis mice can be restored by the laxative polyethylene glycol

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00188.2018 ◽

2019 ◽

Vol 316 (3) ◽

pp. G404-G411 ◽

Cited By ~ 3

Author(s):

Anna Bertolini ◽

Ivo P. van de Peppel ◽

Marcela Doktorova-Demmin ◽

Frank A. J. A. Bodewes ◽

Hugo de Jonge ◽

...

Keyword(s):

Gene Expression ◽

Cystic Fibrosis ◽

Polyethylene Glycol ◽

Bile Acid ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Farnesoid X Receptor ◽

Fibroblast Growth ◽

Gastrointestinal Complications ◽

Osmotic Laxative

The gastrointestinal phenotype of cystic fibrosis (CF) features intestinal bile acid (BA) malabsorption, impaired intestinal farnesoid X receptor (FXR) activation, and consequently reduced fibroblast growth factor 19 (FGF19, FGF15 in mice) production. The osmotic laxative polyethylene glycol (PEG) has been shown to decrease intestinal mucus accumulation in CF mice and could, by doing so, improve BA reabsorption. Here we determined the effect of PEG on BA excretion and FXR-FGF15 signaling in CF mice. Male Cftr−/−tm1Unc (CF) and wild-type (WT) littermates were administered PEG 4000 in drinking water and fed either chow or a semisynthetic diet. PEG was withdrawn for 3 days before termination. Fecal BA excretion was measured at PEG dosages of 37 g/l (100%) and 0 g/l (0%). Ileal FXR activation was assessed by gene expression of its downstream targets Fgf15 and small heterodimer partner ( Shp). In CF mice, PEG withdrawal increased fecal BA excretion on either diet compared with full PEG dosage (chow, 2-fold, P = 0.06; semisynthetic, 4.4-fold, P = 0.007). PEG withdrawal did not affect fecal BA excretion in WT mice on either diet. After PEG withdrawal, gene expression levels of intestinal FXR target genes Fgf15 and Shp were decreased in CF mice but unaffected in WT littermates. PEG did not affect the gene expression of the main intestinal BA transporter apical sodium-dependent bile acid transporter (ASBT). PEG treatment ameliorates intestinal BA malabsorption in CF mice and restores intestinal FXR-FGF15 signaling, independent from Asbt gene expression. These findings highlight the potential of PEG in the prevention and treatment of the gastrointestinal phenotype of CF. NEW & NOTEWORTHY A gastrointestinal feature of cystic fibrosis is bile acid malabsorption and consequent impairment of farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling. FXR-FGF15 signaling regulates various metabolic processes and could be implicated in metabolic and gastrointestinal complications of cystic fibrosis, such as diabetes and liver disease. In cystic fibrosis mice, treatment with the osmotic laxative polyethylene glycol is associated with decreased fecal bile acid loss and restoration of FXR-FGF15 signaling.

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