Chemerin-9-induced contraction was enhanced through the upregulation of smooth muscle chemokine-like receptor 1 in isolated pulmonary artery of pulmonary arterial hypertensive rats

Omori, Ayaho; Goshima, Makoto; Kakuda, Chiharu; Kodama, Tomoko; Otani, Kosuke; Okada, Muneyoshi; Yamawaki, Hideyuki

doi:10.1007/s00424-019-02345-5

Cited by 17 publications

(22 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously showed that chemerin potentiated endothelinmediated vasoconstriction in pulmonary arteries isolated in toto from healthy adult rats (Hanthazi et al, 2019). These data were recently confirmed by Omori et al showing increased chemerin-9-induced pulmonary artery contraction in experimental pulmonary hypertension (Omori et al, 2020). Similarly, we found that chemerin was a co-mitogenic factor for endothelin-1, necessary to allow proliferation in pulmonary artery SMCs.…”

Section: Discussionsupporting

confidence: 86%

“…Alteration in chemerin signaling has already been linked to other pro-inflammatory conditions or cytokines (including TNF-α, IL-1β, and IL-6) upregulating CMKLR1 ( Kaur et al, 2010 ; Bondue et al, 2011 ) and CCRL2 ( Yoshimura and Oppenheim, 2011 ; Monnier et al, 2012 ) which are also known to play crucial roles in pulmonary artery remodeling in pulmonary hypertension. Moreover, this effect was more pronounced for CMKLR1, which is currently known as the main chemerin activity-linked receptor ( Omori et al, 2020 ). Indeed, we know that CCRL2 does not induce the activation of intracellular signaling pathways but regulates chemerin bioavailability ( Zabel et al, 2008 ; Monnier et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chemerin Added to Endothelin-1 Promotes Rat Pulmonary Artery Smooth Muscle Cell Proliferation and Migration

et al. 2020

View full text Add to dashboard Cite

Background: While chemerin has been shown to increase proliferation and migration of systemic vascular smooth muscle cells (SMCs) contributing therefore to the development of hypertension, this remains to be clarified for the pulmonary circulation. Methods: Expression of chemerin and its three receptors (CMKRL1, CCRL2, GPR1) was examined by immunohistochemistry and RTq-PCR in lungs, pulmonary artery, and thoracic aorta from Wistar rats. Primary cultured rat pulmonary artery and thoracic aorta SMCs treated with recombinant chemerin (tested from 5.10 −9 to 10 −7 mol/L) were assessed for proliferation and migration (both with 10 −7 mol/L endothelin-1), as well as for staurosporine-induced apoptosis. Results: In pulmonary artery and thoracic aorta, CMKLR1 expression was detected in both endothelial cells and SMCs. In primary cultured pulmonary artery SMCs, chemerin and its three receptors were expressed, and CMKLR1 expression was higher than those of CCRL2 and GPR1. Chemerin added to endothelin-1 increased pulmonary artery SMC proliferation, while chemerin or endothelin-1 alone did not. This effect was less pronounced in thoracic aorta SMCs. Chemerin induced pulmonary artery and thoracic aorta SMC migration, which was exacerbated by endothelin-1 and more pronounced in thoracic aorta SMCs. Chemerin concentration-dependently reduced staurosporineinduced apoptosis in both pulmonary artery and thoracic aorta SMCs. In pulmonary artery SMCs, endothelin-1 treatment increased the expression of CMKLR1, CCRL2, and GPR1, while these expressions were not altered in thoracic aorta SMCs. Conclusion: Chemerin/CMKRL1 signaling, in conjunction with a key mediator in the pathogenesis of pulmonary hypertensive diseases, endothelin-1, stimulated proliferation and migration, and increased resistance to apoptosis in rat primary cultured pulmonary artery SMCs. Our results suggest that this signaling could play a role in pulmonary artery remodeling observed in pulmonary hypertension.

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Chemerin Added to Endothelin-1 Promotes Rat Pulmonary Artery Smooth Muscle Cell Proliferation and Migration

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Finally, we examined the effects of chemerin-9 on the expression of chemerin and CMKLR1. Results showed that the circulating chemerin and the AAA-tissue chemerin/ CMKLR1 expression were downregulated following the chemerin-9 treatment, contradicting previous studies [24,52]. ese conflicts may be attributed to the different dosages or modes of chemerin-9 administration, or the disparate microenvironment of experimental models.…”

Section: Discussioncontrasting

confidence: 60%

Chemerin-9 Attenuates Experimental Abdominal Aortic Aneurysm Formation in ApoE−/− Mice

Chen

Han

Bian

et al. 2021

Journal of Oncology

View full text Add to dashboard Cite

Chronic inflammation plays an essential role in the pathogenesis of abdominal aortic aneurysm (AAA), a progressive segmental abdominal aortic dilation. Chemerin, a multifunctional adipocytokine, is mainly generated in the liver and adipose tissue. The combination of chemerin and chemokine-like receptor 1 (CMKLR1) has been demonstrated to promote the progression of atherosclerosis, arthritis diseases, and Crohn’s disease. However, chemerin-9 acts as an analog of chemerin to exert an anti-inflammatory effect by binding to CMKLR1. Here, we first demonstrated that AAA exhibited higher levels of chemerin and CMKLR1 expression compared with the normal aortic tissues. Hence, we hypothesized that the chemerin/CMKLR1 axis might be involved in AAA progression. Moreover, we found that chemerin-9 treatment markedly suppressed inflammatory cell infiltration, neovascularization, and matrix metalloproteinase (MMP) expression, while increasing the elastic fibers and smooth muscle cells (SMCs) in Ang II-induced AAA in ApoE−/− mice. This demonstrated that chemerin-9 could inhibit AAA formation. Collectively, our findings indicate a potential mechanism underlying AAA progression and suggest that chemerin-9 can be used therapeutically.

show abstract

“…The protein expressions of chemerin and chemR23 were elevated in PAH model rats. And chemerin-9 (chemR23 agonist) induced contraction of the isolated intrapulmonary artery through increasing chemR23 protein expression in VSMCs [ 123 ]. Although animal experiments indicated that chemerin/chemR23 axis was involved in the development of PAH, there was still a lack of abundant clinical observations to prove this correlation in patients with PAH.…”

Section: Cardiovascular Diseases Mediated By Chemerin/chemr23 Axismentioning

confidence: 99%

“…In comparison with the controls, serum chemerin concentration was observably higher in patients with mild and moderate AV stenosis. Interestingly enough, the patients with the severe stenosis had lower circulating chemerin concentration than those in the mild and moderate stenosis, for which inactivation of inflammation might account [ 123 , 124 ]. So, chemerin was proposed as a good predictor for mild AV stenosis and chemerin > 38.60 ng/mL was selected as the cut-off point for the diagnosis of mild AV stenosis.…”

Section: Cardiovascular Diseases Mediated By Chemerin/chemr23 Axismentioning

confidence: 99%

Role of Chemerin/ChemR23 axis as an emerging therapeutic perspective on obesity-related vascular dysfunction

Xie

Liu

2022

J Transl Med

View full text Add to dashboard Cite

Sufficient epidemiological investigations demonstrate that there is a close correlation between obesity and vascular dysfunction. Nevertheless, specific mechanisms underlying this link remain currently unclear. Given the crucial and decisive role of vascular dysfunction in multitudinous diseases, various hypotheses had been proposed and numerous experiments were being carried out. One recognized view is that increased adipokine secretion following the expanded mass of white adipose tissue due to obesity contributes to the regulation of vascular function. Chemerin, as a neo-adipokine, whose systemic level is elevated in obesity, is believed as a regulator of adipogenesis, inflammation, and vascular dysfunction via binding its cell surface receptor, chemR23. Hence, this review aims to focus on the up-to-date proof on chemerin/chemR23 axis-relevant signaling pathways, emphasize the multifarious impacts of chemerin/chemR23 axis on vascular function regulation, raise certain unsettled questions to inspire further investigations, and explore the therapeutic possibilities targeting chemerin/chemR23.

show abstract

Chemerin-9-induced contraction was enhanced through the upregulation of smooth muscle chemokine-like receptor 1 in isolated pulmonary artery of pulmonary arterial hypertensive rats

Cited by 17 publications

References 26 publications

Chemerin Added to Endothelin-1 Promotes Rat Pulmonary Artery Smooth Muscle Cell Proliferation and Migration

Chemerin Added to Endothelin-1 Promotes Rat Pulmonary Artery Smooth Muscle Cell Proliferation and Migration

Chemerin-9 Attenuates Experimental Abdominal Aortic Aneurysm Formation in ApoE−/− Mice

Role of Chemerin/ChemR23 axis as an emerging therapeutic perspective on obesity-related vascular dysfunction

Contact Info

Product

Resources

About