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Biology subjects

Jebaraj, B.

Publications and source records attributed to Jebaraj, B..

2 recordsLinked to original sources

GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration

GPR15LG, a chemokine-like ligand for the G-protein coupled receptor 15 (GPR15), is abundantly expressed in the gastrointestinal mucosa and inflamed skin. Emerging evidence suggests its involvement in inflammatory disorders and cancers. This study investigates the effects of GPR15LG on the signaling and downstream functions of C-X-C chemokine receptor type 4 (CXCR4), which plays a critical role in immune cell trafficking and cancer metastasis. The results demonstrate that GPR15LG binds to the orthosteric site of CXCR4, modulating downstream signaling in a context-dependent manner. Specifically, GPR15LG enhances CXCL12-mediated CXCR4 signaling synergistically, promoting wound healing and cell migration across various cell types, including CD4+ T cells and cancer cells. These findings underscore the role of GPR15LG in inflammation and metastasis, offering potential therapeutic avenues for CXCR4-mediated diseases. TeaserGPR15LG binds CXCR4 thereby modulating CXCL12/CXCR4 signaling and immune and cancer cell trafficking.

cell biology↗

Vasoconstriction in isolated goat aorta does not increase mean aortic pressure

Vasoconstriction in small arteries and arterioles is known to increase resistance to flow, while vasoconstriction in large arteries and aorta is known to decrease their compliance. Besides this general understanding, there is no systematic documentation on what happens to small artery compliance and large artery resistance during vasoconstriction and the corresponding alterations in vascular pressure. The aim of the study is to assess the effect of adrenaline on goat aortae and small arteries in terms of resistance and compliance. Isolated goat aortae and small arteries were perfused with a pulsatile pump and lumen pressure was recorded before and after addition of adrenaline. In the aortae, systolic pressure increased, diastolic pressure decreased, pulse pressure increased (p = 0.018, WSR); but the mean pressure remained the same (p = 0.357, WSR). Small artery vasoconstriction caused an increase in systolic, diastolic and mean pressures (p = 0.028, WSR). Using length, radius, and thickness data from the tissues and the tubes of the experimental set-up, electrical models were simulated to understand the biological data. The simulations allow us to infer that vasoconstriction in aorta leads to a reduction in compliance, but an increase in resistance if any, is not sufficient to change the mean aortic pressure. On the other hand, vasoconstriction in small arteries increases resistance, but a decrease in compliance if any, does not affect any of the four pressure parameters measured. Vasoconstriction in aorta decreases compliance and therefore increases pulse pressure but does not change resistance significantly enough to alter mean pressure. Key Points SummaryO_LIThe main aim of the study is to understand where exactly resistance (R) and compliance (C) components of the vasculature occur. There is no definitive evidence for the effect of large artery vasoconstriction on resistance and hence the mean arterial pressure. C_LIO_LIThe manuscript presents biological experiments studying the pressure response of goat aorta and small arteries to adrenaline (invitro) and the interpretations using equivalent electrical models. C_LIO_LIThe study shows that in aorta and large arteries, vasoconstriction does not lead to a reduction in lumen diameter sufficient to cause a rise in resistance and mean pressure as compared to small arteries. C_LIO_LIKnowledge of exact location of R and C in the arterial tree enables re-assessment of the differential action of vasoactive drugs on resistance versus compliance vessels once we resolve beat-to-beat R and C changes in response to a drug. This way antihypertensive therapy can be tailored to address the specific cause of the type of hypertension. C_LI

physiology↗