Roles for heterodimerization of APJ and B2R in promoting cell proliferation via ERK1/2-eNOS signaling pathway

Ji, Bingyuan; Shang, Liyan; Wang, Chunmei; Wan, Lei; Cheng, Baohua; Chen, Jing

doi:10.1016/j.cellsig.2020.109671

Cited by 12 publications

(6 citation statements)

References 61 publications

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“…Another study demonstrated strong AR immunoreactivity in the tubular epithelium [28]. In human embryonic kidney (HEK) 293 cells cotransfected with both receptors, the AR was found to form heterodimers with the bradykinin B2 receptor [29].…”

Section: The Expression Of Ar Apelin and Apela In The Kidneymentioning

confidence: 99%

The emerging role of the apelinergic system in kidney physiology and disease

Janssens

Decuypere

Bammens

et al. 2021

Nephrology Dialysis Transplantation

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The apelinergic system (AS) is a novel pleiotropic system with an essential role in renal and cardiovascular physiology and disease, including water homeostasis and blood pressure regulation. It consists of two highly conserved peptide ligands, apelin and apela, and a G-protein-coupled apelin receptor. The two ligands have many isoforms and a short half-life, and exert both similar and divergent effects. Vasopressin, apelin and their receptors colocalize in hypothalamic regions essential for body fluid homeostasis and interact at the central and renal levels to regulate water homeostasis and diuresis in inverse directions. In addition, the AS and renin angiotensin system interact both systemically and in the kidney, with implications for the cardiovascular system. A role for the AS in diverse pathological states, including disorders of sodium and water balance, hypertension, heart failure, pre-eclampsia, acute kidney injury, sepsis and diabetic nephropathy has recently been reported. Furthermore, several metabolically stable apelin analogs have been developed, with potential applications in diverse diseases. We review here what is currently known about the physiological functions of the AS, focusing on renal, cardiovascular and metabolic homeostasis, and the role of the AS in associated diseases. We also describe several hurdles and research opportunities worthy of the attention of the nephrology community.

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Section: The Expression Of Ar Apelin and Apela In The Kidneymentioning

confidence: 99%

The emerging role of the apelinergic system in kidney physiology and disease

Janssens

Decuypere

Bammens

et al. 2021

Nephrology Dialysis Transplantation

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“…A previous study revealed that apelin could reduce blood glucose content by regulating the expression of eNOS and activating the Akt pathway ( 31 ). The expression of apelin could also produce NO by activating APJ, therefore relieving the clinical manifestations of diabetic nephropathy ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Apelin‑13 alleviates diabetic nephropathy by enhancing nitric oxide production and suppressing kidney tissue fibrosis

et al. 2021

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Diabetes is a serious metabolic disease, and the kidney damage induced by diabetes also seriously affects the survival of patients. Apelin is a molecule that plays a crucial role in lipid metabolism, and recent studies have revealed that apelin-13, a subtype of apelin, plays an important role in regulating blood glucose levels. However, the role of apelin-13 in diabetic nephropathy remains unclear. In the present study, a rat model of diabetic nephropathy was constructed by the injection of streptozocin (STZ). During this process, these rats were injected with apelin-13. The blood glucose, urine protein and insulin levels were determined weekly. Next, the expression of angiotensin domain type 1 receptor-associated protein (APJ), endothelial nitric oxide synthase (eNOS), E-cadherin and α-smooth muscle actin (α-SMA) in the kidney tissues was determined with western blotting. Then, the endothelial cells of glomerular vessels were cultured with high glucose medium. These cells were treated with apelin-13 for 24 h. Finally, cell viability of these cells and the expression of APJ, eNOS, E-cadherin and α-SMA in these cells were determined with western blotting. As a result, treatment of apelin-13 induced the lower levels of blood glucose and urine protein.In addition, application of apelin-13 promoted the production of insulin and alleviated the insulin resistance. Treatment with apelin-13 promoted the expression of APJ, eNOS and E-cadherin while it suppressed the expression of α-SMA in kidney tissues of rats and endothelial cells of glomerular vessels. Furthermore, application of apelin-13 also promoted the cell viability of these cells. In conclusion, apelin-13 relieved diabetic nephropathy by promoting the production of nitric oxide (NO) and alleviating the fibrosis of kidney tissues.

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“…APJ is widely expressed in the cardiovascular system. APJ-B2R heterodimers expressed in human umbilical vein endothelial cells (HUVECs) enhance the phosphorylation of eNOS and extracellular signal regulated kinases1/2 (ERK1/2), thus facilitating cell proliferation [ 48 ]. κ-OR is distributed in the nervous system, which is activated by dynorphin (Dyn) and participates in analgesia, fluid homeostasis, and anti-pruritic activity.…”

Section: B2r Functionsmentioning

confidence: 99%

Function and structure of bradykinin receptor 2 for drug discovery

Shen

Zhang

2022

Acta Pharmacol Sin

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Type 2 bradykinin receptor (B2R) is an essential G protein-coupled receptor (GPCR) that regulates the cardiovascular system as a vasodepressor. Dysfunction of B2R is also closely related to cancers and hereditary angioedema (HAE). Although several B2R agonists and antagonists have been developed, icatibant is the only B2R antagonist clinically used for treating HAE. The recently determined structures of B2R have provided molecular insights into the functions and regulation of B2R, which shed light on structure-based drug design for the treatment of B2R-related diseases. In this review, we summarize the structure and function of B2R in relation to drug discovery and discuss future research directions to elucidate the remaining unknown functions of B2R dimerization.

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Roles for heterodimerization of APJ and B2R in promoting cell proliferation via ERK1/2-eNOS signaling pathway

Abstract: Please refer to published version for the most recent bibliographic citation information. If a published version is known of, the repository item page linked to above, will contain details on accessing it.

Cited by 12 publications

References 61 publications

The emerging role of the apelinergic system in kidney physiology and disease

The emerging role of the apelinergic system in kidney physiology and disease

Apelin‑13 alleviates diabetic nephropathy by enhancing nitric oxide production and suppressing kidney tissue fibrosis

Function and structure of bradykinin receptor 2 for drug discovery

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