scholarly journals Cell Type-specific Effect of Hypoxia and Platelet-derived Growth Factor-BB on Extracellular Matrix Turnover and Its Consequences for Lung Remodeling

2006 ◽  
Vol 282 (2) ◽  
pp. 908-915 ◽  
Author(s):  
George Karakiulakis ◽  
Eleni Papakonstantinou ◽  
Alexios J. Aletras ◽  
Michael Tamm ◽  
Michael Roth
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Specific Effect ◽  
Platelet Derived Growth Factor ◽  
Cell Type ◽  
Lung Remodeling ◽  
Cell Type Specific

scholarly journals Cell-type-specific expression of the platelet-derived growth factor alpha receptor: a role for GATA-binding protein.

1996 ◽  
Vol 16 (2) ◽  
pp. 712-723 ◽  
Author(s):  
C Wang ◽  
B Song
Keyword(s):  
Retinoic Acid ◽  
Growth Factor ◽  
Cyclic Amp ◽  
Binding Sites ◽  
Platelet Derived Growth Factor ◽  
Cell Type ◽  
Enhancer Element ◽  
Cell Type Specific ◽  
Factor Alpha ◽  
Parietal Endoderm

Platelet-derived growth factor alpha receptor (PDGF alpha R) is a transmembrane tyrosine kinase receptor for all three existing PDGF isoforms, AA, AB, and BB. Transcripts of PDGF alpha R are detected as early as in fertilized mouse eggs and throughout adulthood in a time- and space-specific manner, thereby suggesting an important role of PDGFs in mammalian development. In this study, we have investigated the mechanism involved in cell-type-specific PDGF alpha R gene expression during early embryonic development. Using F9 embryonic carcinoma cells as an in vitro study model, we identified a differentiation-dependent enhancer element within the PDGF alpha R promoter that controlled receptor expression during parietal endoderm cell differentiation induced by retinoic acid and dibutyryl cyclic AMP treatment. The differentiation-dependent enhancer element sequence bore no resemblance to consensus DNA-binding sites of either the retinoic acid receptor family or the cyclic AMP-responsive element-binding protein family. It was composed of two identical 12-bp direct repeats separated by a 17-bp insert sequence enriched in C and A nucleotides. Although only a single repeat was needed to form specific DNA-protein complexes with factors present in F9 parietal endoderm cell extracts, both repeats together were necessary to display cell-type-specific enhancing activity. Mutational analysis revealed that the protein-binding sites within the repeat sequences were identical to GATA-binding sites. In this study, we provided evidence to suggest that a member of the GATA transcription factor family (GATA-4) is responsible for parietal endoderm-specific PDGF alpha R expression.

Time- and cell type-specific induction of platelet-derived growth factor receptor-β during cerebral ischemia

2003 ◽  
Vol 113 (1-2) ◽  
pp. 44-51 ◽  
Author(s):  
Oliver Renner ◽  
Asterios Tsimpas ◽  
Sawa Kostin ◽  
Samuel Valable ◽  
Edwige Petit ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Cell Type ◽  
Specific Induction ◽  
Cell Type Specific

scholarly journals Identification of a Cell Type-specific Enhancer in the Distal 5′-Region of the Platelet-derived Growth Factor A-chain Gene

1998 ◽  
Vol 273 (50) ◽  
pp. 33239-33246 ◽  
Author(s):  
Raymond S. Maul ◽  
Hongxing Zhang ◽  
James D. Reid ◽  
Nancy G. Pedigo ◽  
David M. Kaetzel
Keyword(s):  
Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Chain Gene ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
A Chain

Cell type-specific requirement of the MAPK pathway for the growth factor action of gastrin

1999 ◽  
Vol 276 (6) ◽  
pp. G1363-G1372 ◽  
Author(s):  
Vinzenz M. Stepan ◽  
Chris J. Dickinson ◽  
John del Valle ◽  
Masashi Matsushima ◽  
Andrea Todisco
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Protein Kinase ◽  
Mapk Pathway ◽  
Cell Type ◽  
Ar42j Cells ◽  
Cell Type Specific ◽  
Ar42j Cell ◽  
Stimulation Of

Gastrin (G17) has a CCKBreceptor-mediated growth-promoting effect on the AR42J rat acinar cell line that is linked to induction of both mitogen-activated protein kinase (MAPK) and c- fos gene expression. We investigated the mechanisms that regulate the growth factor action of G17 on the rat pituitary adenoma cell line GH3. Both AR42J and GH3cells displayed equal levels of CCKBreceptor expression and similar binding kinetics of125I-labeled G17. G17 stimulation of cell proliferation was identical in both cell lines. G17 stimulation of GH3cell proliferation was completely blocked by the CCKBreceptor antagonist D2 but not by the MEK inhibitor PD-98059 or the protein kinase C inhibitor GF-109203X, which completely inhibited G17 induction of AR42J cell proliferation. G17 induced a c- fos SRE-luciferase reporter gene plasmid more than fourfold in the AR42J cells, whereas it had no effect in the GH3cells. In contrast to what we observed in the AR42J cells, G17 failed to stimulate MAPK activation and Shc tyrosyl phosphorylation and association with the adapter protein Grb2. Epidermal growth factor induced the MAPK pathway in the GH3cells, demonstrating the integrity of this signaling system. G17 induced Ca2+mobilization in both the GH3and AR42J cells. The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide inhibited AR42J cell proliferation by 20%, whereas it completely blocked G17 induction of GH3cell growth. The Ca2+ionophore ionomycin stimulated GH3cell proliferation to a level similar to that observed in response to G17, but it had no effect on AR42J cell proliferation. Thus there are cell type specific differences in the requirement of the MAPK pathway for the growth factor action of G17. Whereas in the AR42J cells G17 stimulates cell growth through activation of MAPK and c- fos gene expression, in the GH3cells, G17 fails to activate MAPK, and it induces cell proliferation through Ca2+-dependent signaling pathways. Furthermore, induction of Ca2+mobilization in the AR42J cells appears not to be sufficient to sustain cell proliferation.

scholarly journals Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease

2020 ◽  
Author(s):  
Álvaro Inglés-Prieto ◽  
Nikolas Furthmann ◽  
Samuel Crossman ◽  
Nina Hoyer ◽  
Meike Petersen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Tissue Repair ◽  
Genetic Model ◽  
Human Cells ◽  
Cell Type ◽  
Degenerative Disorders ◽  
Wide Range ◽  
Cell Type Specific

AbstractOptogenetics has been harnessed to shed new mechanistic light on current therapies and to develop future treatment strategies. This has been to date achieved by the correction of electrical signals in neuronal cells and neural circuits that are affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and thereby may modify progression of degenerative disorders, has never been demonstrated in an animal disease model. Here, we reengineered the human and Drosophila melanogaster REarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to overcome limitations of current strategies towards a spatio-temporal regulation of tissue repair.Significance StatementThe death of physiologically important cell populations underlies of a wide range of degenerative disorders, including Parkinson’s disease (PD). Two major strategies to counter cell degeneration, soluble growth factor injection and growth factor gene therapy, can lead to the undesired activation of bystander cells and non-natural permanent signaling responses. Here, we employed optogenetics to deliver cell type-specific pro-survival signals in a genetic model of PD. In Drosophila and human cells exhibiting loss of the PINK1 kinase, akin to autosomal recessive PD, we efficiently suppressed disease phenotypes using a light-activated tyrosine kinase receptor. This work demonstrates a spatio-temporally precise strategy to interfere with degeneration and may open new avenues towards tissue repair in disease models.

scholarly journals Analysis of putative cis-regulatory elements regulating blood pressure variation

2020 ◽  
Vol 29 (11) ◽  
pp. 1922-1932
Author(s):  
Priyanka Nandakumar ◽  
Dongwon Lee ◽  
Thomas J Hoffmann ◽  
Georg B Ehret ◽  
Dan Arking ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Association Studies ◽  
Specific Effect ◽  
Cell Types ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Genome Wide Association Studies ◽  
Cell Type ◽  
Functional Scores ◽  
Cell Type Specific

Abstract Hundreds of loci have been associated with blood pressure (BP) traits from many genome-wide association studies. We identified an enrichment of these loci in aorta and tibial artery expression quantitative trait loci in our previous work in ~100 000 Genetic Epidemiology Research on Aging study participants. In the present study, we sought to fine-map known loci and identify novel genes by determining putative regulatory regions for these and other tissues relevant to BP. We constructed maps of putative cis-regulatory elements (CREs) using publicly available open chromatin data for the heart, aorta and tibial arteries, and multiple kidney cell types. Variants within these regions may be evaluated quantitatively for their tissue- or cell-type-specific regulatory impact using deltaSVM functional scores, as described in our previous work. We aggregate variants within these putative CREs within 50 Kb of the start or end of ‘expressed’ genes in these tissues or cell types using public expression data and use deltaSVM scores as weights in the group-wise sequence kernel association test to identify candidates. We test for association with both BP traits and expression within these tissues or cell types of interest and identify the candidates MTHFR, C10orf32, CSK, NOV, ULK4, SDCCAG8, SCAMP5, RPP25, HDGFRP3, VPS37B and PPCDC. Additionally, we examined two known QT interval genes, SCN5A and NOS1AP, in the Atherosclerosis Risk in Communities Study, as a positive control, and observed the expected heart-specific effect. Thus, our method identifies variants and genes for further functional testing using tissue- or cell-type-specific putative regulatory information.

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