Notch1 and Notch3 coordinate for pericyte-induced stabilization of vasculature

Author(s):  
Juliann B. Tefft ◽  
Jennifer L. Bays ◽  
Alex Lammers ◽  
Sudong Kim ◽  
Jeroen Eyckmans ◽  
...  

The Notch pathway regulates complex patterning events in many species and is critical for the proper formation and function of the vasculature. Despite this importance, how the various components of the Notch pathway work in concert is still not well understood. For example, NOTCH1 stabilizes homotypic endothelial junctions, but the role of NOTCH1 in heterotypic interactions is not entirely clear. NOTCH3, on the other hand, is essential for heterotypic interactions of pericytes with the endothelium, but how NOTCH3 signaling in pericytes impacts the endothelium remains elusive. Here, we use in vitro vascular models to investigate whether pericyte-induced stabilization of the vasculature requires cooperation of NOTCH1 and NOTCH3. We observe that both pericyte NOTCH3 and endothelial NOTCH1 are required for stabilization of the endothelium. Loss of either NOTCH3 or NOTCH1 decreases accumulation of VE-cadherin at endothelial adherens junctions and increases the frequency of wider, more motile junctions. We found that DLL4 was the key ligand for simulating NOTCH1 activation in endothelial cells and observed that DLL4 expression in pericytes is dependent on NOTCH3. Altogether, these data suggest that an interplay between pericyte NOTCH3 and endothelial NOTCH1 is critical for pericyte-induced vascular stabilization.

1977 ◽  
Vol 146 (6) ◽  
pp. 1707-1718 ◽  
Author(s):  
I M Zitron ◽  
D E Mosier ◽  
W E Paul

An alloanti-delta antibody was prepared by immunizing C57BL/Ka mice with BALB/c spleen cells. Its specificity for delta-chain was demonstrated by immunoprecipitation and SDS-PAGE of 125I-labeled membrane proteins from BC8 spleen cells. BC8 mice possess C57BL/Ka "background" genes and BALB/c IgH genes. The anti-delta reagent without complement inhibited the primary in vitro anti-TNP antibody response to TNP-AECM-Ficoll by BC8 spleen cells, although it had no effect of the anti-TNP response of congenic C57BL/Ka spleen cells, which lack the delta-allotype identified by this antibody. On the other hand, the anti-delta antibody had no effect on the anti-TNP response of BC8 spleen cells to TNP-BA, except at limiting antigen concentrations. Both TNP-AECM-Ficoll and TNP-BA are T-I antigens, but they differ in that TNP-AECM-Ficoll fails to stimulate in vitro responses by immunologically defective CBA/N and neonatal spleen cells whereas TNP-BA can cause responses from both these animals. These results suggest that the IgD receptor is critical to T-I antibody responses initiated by TNP-AECM-Ficoll but that it is not required for T-I responses stimulated by TNP-BA.


2021 ◽  
Vol 12 ◽  
Author(s):  
Daphne M. Peelen ◽  
Martin J. Hoogduijn ◽  
Dennis A. Hesselink ◽  
Carla C. Baan

The endothelium plays a key role in acute and chronic rejection of solid organ transplants. During both processes the endothelium is damaged often with major consequences for organ function. Also, endothelial cells (EC) have antigen-presenting properties and can in this manner initiate and enhance alloreactive immune responses. For decades, knowledge about these roles of EC have been obtained by studying both in vitro and in vivo models. These experimental models poorly imitate the immune response in patients and might explain why the discovery and development of agents that control EC responses is hampered. In recent years, various innovative human 3D in vitro models mimicking in vivo organ structure and function have been developed. These models will extend the knowledge about the diverse roles of EC in allograft rejection and will hopefully lead to discoveries of new targets that are involved in the interactions between the donor organ EC and the recipient's immune system. Moreover, these models can be used to gain a better insight in the mode of action of the currently prescribed immunosuppression and will enhance the development of novel therapeutics aiming to reduce allograft rejection and prolong graft survival.


1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.


1974 ◽  
Vol 77 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Gustav Wägar

ABSTRACT Whether the short-term regulation of thyroidal protein synthesis by TSH occurs at the transcriptional or the translational level was tested by measuring the effect of actinomycin D (act D) on the TSH-induced stimulation of L-14C-leucine incorporation into the thyroidal proteins of rats. TSH was injected 6 h before the rats were killed. The thyroid glands were then removed and incubated in vitro in the presence of L-14C-leucine for 2 h. The pronounced stimulation of leucine incorporation in the TSH-treated animals was depressed as compared with controls but still significant even when the animals had been pre-treated with 100 μg act D 24 and 7 h before sacrifice. On the other hand, act D strongly decreased incorporation of 3H-uridine into RNA. Short-term regulation of thyroidal protein synthesis by TSH appears to be partly but not wholly dependent on neosynthesis of RNA. Hence regulation may partly occur at the translation level of protein synthesis.


1973 ◽  
Vol 74 (4) ◽  
pp. 769-774 ◽  
Author(s):  
Akira Yokoyama ◽  
Hiroshi Tomogane ◽  
Katuaki Ôta
Keyword(s):  

ABSTRACT A non-steroidal oestrogen antagonist, MER-25, was administered to cycling rats for elucidating the role of oestrogen in the surge of prolactin observed on the afternoon of pro-oestrus (POe). In animals injected with 20 mg of MER-25 intramuscularly on the afternoon (16.30 h) of the first day of dioestrus (D-1), the surge of prolactin was blocked while the level of prolactin on the afternoon of POe of these animals was significantly higher than that of the corresponding controls injected with oil. Ovulation was also blocked in these animals treated with the drug on the afternoon of D-l. On the other hand, treatment on the morning (10.30 h) of the 2nd day of dioestrus failed to prevent not only the surge of prolactin but also ovulation. These observations provide strong evidence for the view that oestrogen is responsible for the surge of prolactin on the afternoon of POe, and that the surge is accompanied by that of LH.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 171-174
Author(s):  
Tarare Toshida ◽  
Chaple Jagruti

The covid-19 resulted in broad range of spread throughout the world in which India has also became a prey of it and in this situation the means of media is extensively inϑluencing the mentality of the people. Media always played a role of loop between society and sources of information. In this epidemic also media is playing a vital role in shaping the reaction in ϑirst place for both good and ill by providing important facts regarding symptoms of Corona virus, preventive measures against the virus and also how to deal with any suspect of disease to overcome covid-19. On the other hand, there are endless people who spread endless rumours overs social media and are adversely affecting life of people but we always count on media because they provide us with valuable answers to our questions, facts and everything in need. Media always remains on top of the line when it comes to stop the out spread of rumours which are surely dangerous kind of information for society. So on our side we should react fairly and maturely to handle the situation to keep it in the favour of humanity and help government not only to ϑight this pandemic but also the info emic.


1987 ◽  
Vol 52 (9) ◽  
pp. 2317-2325 ◽  
Author(s):  
Jan Hlaváček ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Walter Y. Chan ◽  
Victor J. Hruby

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.


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