APLN/APJ pathway: The key regulator of macrophage functions

Arababadi, Mohammad Kazemi; Asadikaram, Parisa; Asadikaram, Gholamreza

doi:10.1016/j.lfs.2019.116645

Cited by 7 publications

(3 citation statements)

References 67 publications

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“…Çelik et al [23] confirmed that apelin induces macrophage polarization towards M2. Arababadi et al [24] reviewed apelin’s impact on macrophages, while Leeper et al [25] highlighted its role in inhibiting macrophage inflammation. Numerous studies have investigated the inflammatory aspects of apelin, yet exploration of its effects on inflammation in renal ischemiareperfusion injury is lacking.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Apelin-13 alleviate inflammatory reaction of ischemia reperfusion in rat kidney transplantation via NF-kappa B signaling pathway

Capelli,

Aiello,

Gasperoni

et al. 2024

Preprint

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Backgroud: Kidney transplantation is the optimal treatment for end-stage renal disease, yet acute rejection remains a significant challenge to the survival rates of grafts. Ischemia-reperfusion injury (IRI) can initiate an inflammatory response that severely damages the transplanted kidney. Methods: The APJ/apelin system has been shown to play an anti-inflammatory role across various domains, and in this study, we utilized apelin-13 in a rat kidney transplantation model to investigate its effects on IRI-related inflammation. Results: Our findings indicate that apelin predominantly localizes in the renal cortex, and following kidney transplantation, there was destruction of tissue structure and an inflammatory response targeting the transplanted kidney. The administration of apelin-13 led to improved kidney function, reduced organizational structure damage, and lower injury and apoptosis indices compared to the control group. Notably, following the administration of apelin-13, the expression levels of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, were reduced in comparison to the model control group, as determined by immunofluorescence, western blot, and ELISA Manuscript File Click here to view linked References assays. Furthermore, the extent of CD3 T cell infiltration was lower relative to that in the model control group. We specifically examined the classical inflammation signaling pathway, NF-κB. Our results show that, compared to the model group, the administration of apelin-13 reduced the expression of NF-κB signaling pathway proteins, as evidenced by both immunohistochemistry and western blot analyses. Conclusions: In conclusion, apelin-13 appears to reduce the inflammatory response to ischemia-reperfusion injury following kidney transplantation, partly through the NF-κB signaling pathway.

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Apelin-13 alleviate inflammatory reaction of ischemia reperfusion in rat kidney transplantation via NF-kappa B signaling pathway

Capelli,

Aiello,

Gasperoni

et al. 2024

Preprint

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“…Increased apelin expression has been found in cardiovascular tissues such as cardiomyocytes, endothelial cells, and vascular smooth muscle cells [ 47 ]. The apelin–APJ axis plays an important role in the cardiovascular system [ 48 , 49 ]. Additionally, apelin has recently been implicated in the physiology of cardiovascular system in regard to cardiac contractility, endothelium-dependent vasodilation, and the reduction of vascular wall inflammation [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Apelin and its ratio to lipid factors are associated with cardiovascular diseases: A systematic review and meta-analysis

et al. 2022

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Background The present systematic review and meta-analysis aimed to ascertain if the circulating levels of apelin, as an important regulator of the cardiovascular homeostasis, differ in patients with cardiovascular diseases (CVDs) and controls. Methods A comprehensive search was performed in electronic databases including PubMed, Scopus, EMBASE, and Web of Science to identify the studies addressing apelin in CVD up to April 5, 2021. Due to the presence of different units to measure the circulating levels of apelin across the included studies, they expressed the standardized mean difference (SMD) and their 95% confidence interval (CI) as summary effect size. A random-effects model comprising DerSimonian and Laird method was used to pool SMDs. Results Twenty-four articles (30 studies) comprised of 1793 cases and 1416 controls were included. Pooled results obtained through random-effects model indicated that apelin concentrations in the cases’ blood samples were significantly lower than those of the control groups (SMD = -0.72, 95% CI: -1.25, -0.18, P = 0.009; I2 = 97.3%, P<0.001). New combined biomarkers showed a significant decrease in SMD of apelin/high-density lipoprotein cholesterol (apelin/HDL-C) ratio [-5.17; 95% CI, -8.72, -1.63, P = 0.000; I2 = 99.0%], apelin/low-density lipoprotein cholesterol (apelin/LDL-C) ratio [-4.31; 95% CI, -6.08, -2.55, P = 0.000; I2 = 98.0%] and apelin/total cholesterol (apelin/TC) ratio [-17.30; 95% CI, -22.85, -11.76, P = 0.000; I2 = 99.1%]. However, no significant differences were found in the SMD of apelin/triacylglycerol (apelin/TG) ratio in cases with CVDs compared to the control group [-2.96; 95% CI, -7.41, 1.49, P = 0.000; I2 = 99.2%]. Conclusion The association of apelin with CVDs is different based on the region and disease subtypes. These findings account for the possible usefulness of apelin as an additional biomarker in the diagnosis of CVD in diabetic patients and in the diagnosis of patients with CAD. Moreover, apelin/HDL-c, apelin/LDL-c, and apelin/TC ratios could be offered as diagnostic markers for CVD.

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“…Apelin, acting via the apelin receptor (APLNR), is considered anti-inflammatory and plays a significant role in the development and function of macrophages [ 109 ]. Apelin downregulates the expression of TNF-α and IL-6 and reduces phagocytic activity in rat peritoneal macrophages in vitro [ 110 ].…”

Section: Adipokines Inflammation and Msmentioning

confidence: 99%

Adipokines as Immune Cell Modulators in Multiple Sclerosis

Rijnsburger

Djuric

Mulder

et al. 2021

IJMS

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Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system (CNS), is a major clinical and societal problem, which has a tremendous impact on the life of patients and their proxies. Current immunomodulatory and anti-inflammatory therapies prove to be relatively effective; however, they fail to concomitantly stop ongoing neurological deterioration and do not reverse acquired disability. The proportion to which genetic and environmental factors contribute to the etiology of MS is still incompletely understood; however, a recent association between MS etiology and obesity was shown, with obesity greatly increasing the risk of developing MS. An altered balance of adipokines, which are white adipose tissue (WAT) hormones, plays an important role in the low-grade chronic inflammation during obesity by their pervasive modification of local and systemic inflammation. Vice versa, inflammatory factors secreted by immune cells affect adipokine function. To explore the role of adipokines in MS pathology, we will here review the reciprocal effects of adipokines and immune cells and summarize alterations in adipokine levels in MS patient cohorts. Finally, we will discuss proof-of-concept studies demonstrating the therapeutic potential of adipokines to target both neuroinflammation and neurodegeneration processes in MS.

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APLN/APJ pathway: The key regulator of macrophage functions

Cited by 7 publications

References 67 publications

WITHDRAWN: Apelin-13 alleviate inflammatory reaction of ischemia reperfusion in rat kidney transplantation via NF-kappa B signaling pathway

WITHDRAWN: Apelin-13 alleviate inflammatory reaction of ischemia reperfusion in rat kidney transplantation via NF-kappa B signaling pathway

Apelin and its ratio to lipid factors are associated with cardiovascular diseases: A systematic review and meta-analysis

Adipokines as Immune Cell Modulators in Multiple Sclerosis

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