scholarly journals Expression of PDE11A in Normal and Malignant Human Tissues

2005 ◽  
Vol 53 (7) ◽  
pp. 895-903 ◽  
Author(s):  
Michael R. D'Andrea ◽  
Yuhong Qiu ◽  
Donna Haynes-Johnson ◽  
Sheela Bhattacharjee ◽  
Patricia Kraft ◽  
...  

Cyclic nucleotide phosphodiesterase 11A (PDE11A) is the newest member in the PDE family. Although the tissue distribution of PDE11A mRNA has been shown, its protein expression pattern has not been well studied. The goal of this report is to investigate the distribution of PDE11A proteins in a wide range of normal and malignant human tissues. We utilized a polyclonal antibody that recognized all four PDE11A isoforms. Its specificity was demonstrated by Western blot analysis on a recombinant human PDE11A protein and native PDE11A proteins in various human tissues. Immunohistochemistry showed that PDE11A is widely expressed. Various degrees of immunoreactivity were observed in the epithelial cells, endothelial cells, and smooth muscle cells of all tissues examined. The highest expression was in the epithelial, endothelial, and smooth muscle cells of the prostate, Leydig, and spermatogenic cells of the testis, the tubule epithelial cells in the kidney, the epithelial and endothelial cells in the adrenal, the epithelial cells and macrophages in the colon, and the epidermis in the skin. Furthermore, PDE11A expression was also detected in several human carcinomas. Our results suggest that PDE11A might be involved in multiple physiological processes in various organs via its ability to modulate intracellular cAMP and cGMP levels.

2009 ◽  
Vol 1209 ◽  
Author(s):  
Lijuan Zhang ◽  
Young Wook chun ◽  
Thomas J Webster

AbstractPLGA (poly-lactic-co-glycolic acid) has been widely used as a biomaterial in regenerative medicine due to its biocompatibility and biodegradability properties. Previous studies have shown that cells (such as bladder smooth muscle cells, chondrocytes, osteoblasts, and vascular smooth muscle cells) respond differently to nano-structured PLGA surfaces (such as those with surface features less than 100 nm in at least one dimension) compared to nano-smooth surfaces. The purpose of the present in vitro research was to prepare PLGA films with various nanometer surface features and determine, for the first time, whether lung cancer epithelial cells respond differently to such topographies. Poly(dimethylsiloxane) (PDMS) molds prepared by placing PDMS onto various polystyrene monolayers and two solution evaporation methods were used to create nanometer surface features on PLGA. The intended spherical surface nano-topographies on PLGA with RMS values of 2.23, 5.03, 5.42 and 36.90 nm were formed, while PLGA surfaces with RMS values of 0.62 and 2.23 nm were obtained by different solution evaporation methods. Most importantly, lung cancer epithelial cells adhered less on the PLGA surfaces with an RMS value of 0.62, 2.23 and 5.42 nm after 4 hours of culture compared to any other PLGA surface created here. After three days, PLGA surfaces with an RMS value of 0.62 nm had much lower cell density than any other sample. In this manner, PLGA with specific nanometer surface features may inhibit lung cancer cell density which may provide for an important biomaterial for the treatment of lung cancer for a wide range of applications (from drug delivery to regenerative medicine).


Endocrinology ◽  
1999 ◽  
Vol 140 (4) ◽  
pp. 1920-1926 ◽  
Author(s):  
Ahmad Shabisgh ◽  
Nozomu Tanji ◽  
Vivette D’Agati ◽  
Martin Burchardt ◽  
Mark Rubin ◽  
...  

Abstract Recent studies have found that blood flow to the rat ventral prostate gland is drastically reduced at an early time after castration. These observations caused us to reevaluate the effects of castration on the various cell populations of the ventral prostate, especially those in the prostatic vascular system. Sections of ventral prostate glands obtained at different times after castration were analyzed using the TUNEL (terminal deoxynucleotide transferase-mediated dUTP nick END labeling) staining method to quantify apoptosis in different cell types. The results of this analysis showed a significant increase in TUNEL staining of prostate endothelial and (nonendothelial) stromal cells as early as 12 h postcastration that continued to 24 h after castration. In contrast, TUNEL labeling of prostate epithelial cells was not significantly increased compared with control values until 72 h after castration. The use of dual immunohistochemical staining procedures (anti-CD31 for endothelial cells or antismooth muscle actin for smooth muscle cells combined with TUNEL labeling) allowed us to confirm that the TUNEL-positive vascular cells at these early times after castration were endothelial in nature, whereas smooth muscle cells surrounding the prostate glands or portions of the afferent vascular endothelium were rarely TUNEL labeled. Electron microscopic evaluation of ventral prostate tissues at 48 h after castration provided further morphological evidence for the occurrence of apoptosis in prostate endothelial cells. Finally, the Lendrum-Fraser histochemical procedure used to identify fibrin leakage in tissues with vascular damage was applied to sections of the ventral prostate gland. This stain revealed diffuse fibrin accumulation in periglandular areas outside the capillaries and blood vessels in prostates from 24-h castrated rats, but not in prostates of sham-operated rats. Our results confirm an early effect of castration on the vascular system of the rat ventral prostate identified by increased apoptosis of endothelial cells and vascular leakiness. As these changes temporally precede the loss of epithelial cells, we propose that they may be causal rather than incidental to regression of the rat ventral prostate after castration.


Author(s):  

In recent years, globally there is an incredible boost in stem cell research has kindled the expectations of both patients and physicians. Mesenchymal stem cells (MSCs) seem to represent a future powerful tool in regenerative medicine, owing to their availability, ease of manipulation, and therapeutic potential, therefore they are particularly important in medical research. Mesenchymal stem cells (MSCs) are capable self-renewing, multipotent progenitor cells with multilineage potential to differentiate into cell types, such as adipocytes, cardiomyocytes, endothelial cells and vascular smooth muscle cells, although the relative contribution of trilineage differentiation and paracrine effectors on cardiac repair. MSCs shows to have the beneficial effects of MSC-based therapies offers most attractive options to treatment of wide range of diseases from cartilage defects to cardiac disorders. Cardiovascular diseases (CVDs) are an important cause of death and disease worldwide. Because injured cardiac tissue cannot be repaired itself, it is urgent to develop other alternate therapies. Stem cells can be differentiated into cardiomyocytes, endothelial cells, and vascular smooth muscle cells for the treatment of CVDs. In addition to cardiac stem cells, mesenchymal stem cells represent another multipotent cell population in the heart; these cells are located in regions near pericytes and exhibit regenerative, angiogenic, antiapoptotic, and immunosuppressive properties.


1994 ◽  
Vol 72 (01) ◽  
pp. 044-053 ◽  
Author(s):  
N Chomiki ◽  
M Henry ◽  
M C Alessi ◽  
F Anfosso ◽  
I Juhan-Vague

SummaryIndividuals with elevated levels of plasminogen activator inhibitor type 1 are at risk of developing atherosclerosis. The mechanisms leading to increased plasma PAI-1 concentrations are not well understood. The link observed between increased PAI-1 levels and insulin resistance has lead workers to investigate the effects of insulin or triglyceride rich lipoproteins on PAI-1 production by cultured hepatocytes or endothelial cells. However, little is known about the contribution of these cells to PAI-1 production in vivo. We have studied the expression of PAI-1 in human liver sections as well as in vessel walls from different territories, by immunocytochemistry and in situ hybridization.We have observed that normal liver endothelial cells expressed PAI-1 while parenchymal cells did not. However, this fact does not refute the role of parenchymal liver cells in pathological states.In healthy vessels, PAI-1 mRNA and protein were detected primarily at the endothelium from the lumen as well as from the vasa vasorum. In normal arteries, smooth muscle cells were able to produce PAI-1 depending on the territory tested. In deeply altered vessels, PAI-1 expression was observed in neovessels scattering the lesions, in some intimal cells and in smooth muscle cells. Local increase PAI-1 mRNA described in atherosclerotic lesions could be due to the abundant neovascularization present in the lesion as well as a raised expression in smooth muscle cells. The increased PAI-1 in atherosclerosis could lead to fibrin deposit during plaque rupture contributing further to the development and progression of the lesion.


1982 ◽  
Vol 48 (01) ◽  
pp. 101-103 ◽  
Author(s):  
B Kirchhof ◽  
J Grünwald

SummaryEndothelial and smooth muscle cells cultured from minipig aorta were examined for their inhibitory activity on thrombin and for their thrombin generating capacity.Endothelial cells showed both a thrombin inhibition and an activation of prothrombin in the presence of Ca++, which was enhanced in the presence of phospholipids. Smooth muscle cells showed an activation of prothrombin but at a lower rate. Both coagulation and amidolytic micro-assays were suitable for studying the thrombin-vessel wall interaction.


1985 ◽  
Vol 53 (02) ◽  
pp. 165-169 ◽  
Author(s):  
Walter E Laug

SummaryTPure cultures of bovine endothelial cells (EC) produce and secrete large amounts of plasminogen activators (PA). Cocultivation of EC with vascular smooth muscle cells (SMC) resulted in a significant decrease of PA activities secreted by the EC, whereas the cellular PA activities remained unaffected. Secreted PA activities were absent in the growth medium as long as the SMC to EC ratio was 2:1 or higher. The PA inhibitory activity of the SMC was rapid and cell-to-cell contact was not necessary.The PA inhibitory activity was present in homogenates of SMC as well as in the medium conditioned by them but not in the extracellular matrix elaborated by these cells. Serum free medium conditioned by SMC neutralized both tissue type (t-PA) and urokinase like (u-PA) plasminogen activators. Gel electrophoretic analysis of SMC conditioned medium followed by reverse fibrin autography demonstrated PA inhibitory activities in the molecular weight (Mr) range of 50,000 to 52,000 similar to those present in media conditioned by bovine endothelial cells or fibroblasts. Regular fibrin zymography of SMC conditioned medium incubated with u-PA or t-PA revealed the presence of a component with a calculated approximate Mr of 45,000 to 50,000 which formed SDS resistant complexes with both types of PA.These data demonstrate that vascular SMC produce and secrete (a) inhibitor(s) of PAs which may influence the fibrinolytic potential of EC.


1995 ◽  
Vol 15 (7) ◽  
pp. 949-955 ◽  
Author(s):  
Jennifer R. Gamble ◽  
Sandy Bradley ◽  
Leanne Noack ◽  
Mathew A. Vadas

1996 ◽  
Vol 16 (10) ◽  
pp. 1263-1268 ◽  
Author(s):  
Antonio López Farré ◽  
Juan R. Mosquera ◽  
Lourdes Sánchez de Miguel ◽  
Inmaculada Millás ◽  
Trinidad de Frutos ◽  
...  

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