Factor Receptor Alpha Expression Research Articles

Analysis of platelet-derived growth factor receptor alpha expression in adult mouse testis

Analysis of platelet-derived growth factor receptor alpha expression in adult mouse testis

Parenchymal Platelet‐Derived Growth Factor Receptor Alpha Expression Is Dispensable For Hepatic Fibrosis During Chronic Liver Injury

Platelet‐derived growth factor receptor a (PDGFRa) is a tyrosine kinase receptor with roles in cell survival, proliferation, and differentiation, and is involved in liver development, regeneration, hepatic fibrosis and cirrhosis. While myofibroblasts derived from hepatic stellate cells and portal fibroblasts are the primary mediators of fibrosis, hepatocytes contribute to disease progression through cell death, release of cytokines and growth factors to influence myofibroblast activation, and by undergoing proliferation for regeneration. However the potential expression and function of PDGFRa in hepatocytes in the setting of chronic liver injury is unclear. In this study we investigate the role of hepatocyte PDGFRα in two murine models of chronic liver injury representing toxic (carbon tetrachloride, CCl4) and cholestatic injury (bile duct ligation, BDL). We show that PDGFRa is up‐regulated in a subset of hepatocytes in murine livers following BDL as well as following chronic CCl4 administration. Next, we generated liver‐specific PDGFRα knockout (KO) mice by interbreeding PDGFRa‐floxed and FoxA3‐cre mice. We show that following 4 weeks of CCl4 treatment, PDGFRα loss in epithelial cells did not affect the development of hepatic fibrosis. Intriguingly, comparably higher levels of PDGFRa were evident in KO and controls after 4 weeks of CCl4. In addition comparable liver injury was evident in KO and controls as assessed by serum biochemistry. Our findings suggest that PDGFRα in hepatic parenchymal cells may not be playing an important role in disease pathogenesis especially at 4 weeks after CCl4. This study also suggests that PDGFRα is primarily expressed in non‐parenchymal cell populations early during chronic liver injury.

Immunohistochemical examination of effects of kefir, koumiss and commercial probiotic capsules on platelet derived growth factor-c and platelet derived growth factor receptor-alpha expression in mouse liver and kidney

We investigated using immunohistochemistry the effects of kefir, koumiss and commercial probiotic capsules on the expression of platelet derived growth factor-c (PDGF-C) and platelet derived growth factor receptor-alpha (PDGFR-α) in mouse liver and kidney. Mice were assigned to four groups: group 1 was given commercial probiotic capsules, group 2 was given kefir, group 3 was given koumiss and group 4 was untreated. After oral administration for 15 days, body weights were recorded and liver and kidney tissue samples were obtained. Hematoxylin and eosin staining was used to examine histology. PDGF-C and PDGFR-α in liver and kidney were localized using the streptavidin-biotin peroxidase complex method (ABC). We found that the weights of the mice in the kefir, koumiss and commercial probiotic capsules groups increased compared to the control group. No differences in liver and kidney histology were observed in any of the experimental groups. Kefir, koumiss and the commercial probiotic preparation increased PDGF-C and PDGFR-α expression.

Platelet‐derived growth factor receptor alpha expression improves the diagnostic assessment of gastrointestinal stromal tumours

HistopathologyVolume 61, Issue 6 p. 1240-1245 Platelet-derived growth factor receptor alpha expression improves the diagnostic assessment of gastrointestinal stromal tumours Elena Tamborini, Elena Tamborini Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalySearch for more papers by this authorSabrina Rossi, Sabrina Rossi Department of Pathology General Hospital of Treviso, ItalySearch for more papers by this authorEva Tarantino, Eva Tarantino Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalySearch for more papers by this authorValentina Mauro, Valentina Mauro Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalySearch for more papers by this authorAngelo P Dei Tos, Angelo P Dei Tos Department of Pathology General Hospital of Treviso, ItalySearch for more papers by this authorSilvana Pilotti, Silvana Pilotti Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalySearch for more papers by this author Elena Tamborini, Elena Tamborini Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalySearch for more papers by this authorSabrina Rossi, Sabrina Rossi Department of Pathology General Hospital of Treviso, ItalySearch for more papers by this authorEva Tarantino, Eva Tarantino Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalySearch for more papers by this authorValentina Mauro, Valentina Mauro Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalySearch for more papers by this authorAngelo P Dei Tos, Angelo P Dei Tos Department of Pathology General Hospital of Treviso, ItalySearch for more papers by this authorSilvana Pilotti, Silvana Pilotti Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalySearch for more papers by this author First published: 18 June 2012 https://doi.org/10.1111/j.1365-2559.2012.04345.xCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume61, Issue6December 2012Pages 1240-1245 RelatedInformation

Post-Transcriptional Regulation of Osteoblastic Platelet-Derived Growth Factor Receptor-Alpha Expression by Co-Cultured Primary Endothelial Cells

Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in osteoblast function. Inhibition of PDGFR activity leads to a suppression of osteoblast proliferation, whereas mineralized matrix production is enhanced. In previous experiments, we showed that co-cultivation of human primary endothelial cells and human primary osteoblasts (hOBs) leads to a cell contact-dependent downregulation of PDGFR-α expression in the osteoblasts. In this study, we investigated this effect in more detail, revealing that human umbilical vein endothelial cell (HUVEC)-mediated PDGFR-α downregulation is dependent on time and cell number. This effect was specific to endothelial cells and was not observed when hOBs were co-cultured with human primary chondrocytes or fibroblasts. Likewise, HUVEC-mediated suppression of PDGFR-α expression was only seen in hOBs and mesenchymal stem cells but not in immortalized osteoblastic cell lines. Functional inhibition of gap junctional communication between HUVECs and hOBs by 18α-glycyrrhetinic acid had no effect on HUVEC-mediated PDGFR-α downregulation, whereas inhibition of p38 mitogen-activated protein kinase (MAPK) prevented the HUVEC-mediated reduction in osteoblastic PDGFR-α expression. To delineate the molecular mechanism underlying the PDGFR-α downregulation, we examined the effect of HUVEC co-cultivation on osteoblastic PDGFR-α promoter activity as well as mRNA stability. Co-cultivation of HUVECs with hOBs significantly shortened the half-life of osteoblastic PDGFR-α mRNA, but did not decrease its promoter activity. In summary, our data show that PDGFR-α is downregulated in hOBs by co-cultivation with human primary endothelial cells through a p38 MAPK-dependent post-transcriptional mechanism.

Mesenchymal cells are required for functional development of thymic epithelial cells

Epithelial-mesenchymal interactions have essential roles in thymus organogenesis. Mesenchymal cells are known to be required for epithelial cell proliferation. However, the contribution of mesenchymal cells to thymic epithelial cell differentiation is still unclear. In the present study, we have investigated the roles of mesenchymal cells in functional development of epithelial cells in the thymus anlage in patch (ph) mutant mice, which have a primarily defect in mesenchymal cells caused by the absence of platelet-derived growth factor receptor alpha expression. In the ph/ph thymus anlage, T cell progenitors migrate normally among the epithelial cells, however, they are severely impaired to proliferate and differentiate to CD25-positive cells. Epithelial cells of the ph/ph thymus anlage show severely impaired proliferation and expression of functional molecules, such as SCF, Delta-like 4 and MHC class II, which have crucial roles in T cell development. Moreover, the cultured ph/ph thymus anlage fails to develop into a mature organ supporting full T cell development. Addition of intact thymic mesenchymal cells to organ culture induces development of the ph/ph thymus anlage. In the cultured lobes, added mesenchymal cells contribute to form not only the capsule but also the meshwork structure mingled with epithelial cells. Our present results strongly suggest the roles of mesenchymal cells in functional development of epithelial cells in thymus organogenesis. In addition, our data suggest that mesenchymal cells are required to create the thymic microenvironment and to maintain epithelial architecture and function.

Immunohistochemical localization of ciliary neurotrophic factor receptor alpha expression in the rat nervous system

Ciliary neurotrophic factor receptor alpha (CNTFR alpha) is essential for normal embryonic development and may be involved in postnatal and adult neuronal maintenance. In addition, a rapidly growing body of evidence suggests that CNTFR alpha serves as a site of action for future growth factor therapeutics capable of treating a wide variety of disorders resulting from neuronal loss. We raised two polyclonal, anti-CNTFR alpha antisera against synthetic peptides corresponding to independent regions of rat CNTFR alpha. Western blot and immunohistochemical analyses indicated that affinity-purified preparations of both antisera specifically recognize CNTFR alpha. In the adult brain, the highest levels of CNTFR alpha immunoreactivity were found in the perikarya, dendrites and, occasionally, the axons of several distinct classes of neurons including hippocampal formation neurons, some sensory neurons, and many neurons involved in motor control. CNTFR alpha immunoreactivity also was concentrated in the following: perikarya, dendrites, and axons of ventral horn motor neurons in adult spinal cord; perikarya and axons of adult dorsal root ganglion neurons; and axons in adult peripheral nerve. In embryonic tissue, the highest levels of CNTFR alpha immunoreactivity were observed in differentiating neurons and their processes. Therefore, the present data suggest that CNTFR alpha serves several diverse functions in adulthood and during development.

Cationic Lipid Is Not Required for Uptake and Selective Inhibitory Activity of ICAM-1 Phosphorothioate Antisense Oligonucleotides in Keratinocytes

Keratinocyte intercellular adhesion molecule-1 (ICAM-1) is important in mediating retention of T cells within the epidermal compartment. To determine if antisense oligonucleotides designed to hybridize to various ICAM-1 mRNA regions could selectively influence cultured keratinocyte ICAM-1 expression following gamma interferon (IFN-gamma), cells were exposed to several antisense compounds, in the absence and presence of cationic lipid (lipofectin). Keratinocytes rapidly internalized sense and antisense compounds (within 30-60 min), even in the absence of lipofectin with approximately 30% of the cell possessing positive nuclei. Such nuclear accumulation was not observed in the absence of lipofectin in cultured fibroblasts, smooth muscle cells, or endothelial cells, even though total cellular uptake within the cytoplasm was significantly increased in all these cell types. Using flow cytometry, IFN-gamma-inducible ICAM-1 expression was reduced 50% by antisense compounds with lipofectin, and by 30% without lipofectin. This inhibition was specific as no change was observed for HLA-DR or tumor necrosis factor-alpha receptor expression. Northern blot hybridization studies confirmed that ICAM-1 antisense oligonucleotides selectively and significantly inhibited ICAM-1 expression. These results suggest that such antisense compounds interact with keratinocytes differently than other cell types, and provide the in vitro basis for clinical trials in which reduction (or elimination) of ICAM-1 expression by epidermal keratinocytes could be selectively accomplished without necessarily influencing dermal cell types such as fibroblasts, endothelial cells, or smooth muscle cells.

IL-1 and transforming growth factor-beta inhibit platelet-derived growth factor-AA binding to osteoblastic cells by reducing platelet-derived growth factor-alpha receptor expression.

Platelet-derived growth factor (PDGF) is thought to play a significant role in bone repair and regeneration. We previously demonstrated that PDGF-AA-induced chemotaxis and proliferation can be modulated by IL-1. We now report that IL-1 and transforming growth factor-beta (TGF-beta) significantly decrease the number of PDGF-AA binding sites in both normal and tumor-derived human osteoblastic cells, whereas PDGF-BB binding is minimally affected. The affinity of PDGF-AA binding remains unchanged in the presence of IL-1, but is slightly reduced by TGF-beta as demonstrated by Scatchard analysis. We also showed that tyrosyl kinase phosphorylation after PDGF-AA binding is decreased in the presence of both IL-1 and TGF-beta. Northern blot analysis indicates that both IL-1 and TGF-beta decrease the expression of PDGF-alpha receptor mRNA. These results suggest that IL-1 and TGF-beta have the potential to regulate PDGF-AA-induced biologic activity in normal human osteoblastic cells and in human osteoblastic sarcoma cells by decreasing the levels of the PDGF-alpha receptor.

Increased tumor necrosis factor-alpha receptor number in chronic hepatitis B virus infection.

Production of the antiviral cytokine, tumor necrosis factor-alpha is increased in chronic hepatitis B virus infection, and clinical studies of tumor necrosis factor-alpha have indicated a proviral effect at higher doses. To determine whether this might be related to abnormal cell surface tumor necrosis factor-alpha receptor expression, binding characteristics of cell surface tumor necrosis factor-alpha receptor on peripheral blood mononuclear cells in chronic hepatitis B virus carriers were studied using radioiodinated recombinant tumor necrosis factor-alpha. The specific binding curves generated were analyzed according to the method of Scatchard to determine cell surface receptor numbers and dissociation constants. A single class of cell surface tumor necrosis factor-alpha receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets. The median number (range) of cell surface tumor necrosis factor-alpha receptors on peripheral blood mononuclear cells from controls (n = 11), chronic hepatitis B virus patients seropositive for hepatitis B virus DNA (n = 8) and seronegative for hepatitis B virus DNA (n = 8) were 2,329 (range = 1,538 to 3,133), 3,375 (range = 2,300 to 6,718) (p less than 0.01) and 3,113 (range = 2,229 to 5,246) (p less than 0.05) sites/cell, respectively. They all had similar dissociation constants of 8.4 x 10(-10) mol/L (range = 4.1 to 16.9), respectively. Further dissection of the peripheral blood mononuclear cells showed that this increase in cell surface receptor number was confined to the monocyte fraction (p less than 0.01). Plasma tumor necrosis factor-alpha levels in five patients with increased monocyte cell surface tumor necrosis factor-alpha receptor numbers were also elevated.(ABSTRACT TRUNCATED AT 250 WORDS)