Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBPɑ axis and inducing M1 macrophage polarization

Ji, Zhisong; Jiang, Hua; Xie, Yue; Wei, Qipeng; Yin, Xiaofang; Ye, Jinhai; Quan, Xiaozhen; Luo, Yanli; Zhao, Meng; Tian, Xiaolong; Zhang, Yajun; Yang, Xuezhou

doi:10.1007/s10565-021-09636-7

Cited by 25 publications

(13 citation statements)

References 42 publications

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“…Regarding chemerin signaling, all VSMC phenotypes secreted chemerin (encoded by RARRES2), and then chemerin was received by chemerin chemokine-like receptor 1 (CMKLR1) in macrophages. Chemerin–CMKLR1 pair stimulated macrophage transformation to the M1 (proinflammatory) subtype via the p-Akt/CEBPα axis ( 39 ) and mediated the migration of macrophages and dendritic cells ( 40 ). Collectively, signaling complement and chemerin mainly promoted macrophage migration, thereby aggravating aortic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Intercellular Communication Between Immune Cells and Altered Vascular Smooth Muscle Cell Phenotypes in Aortic Aneurysm From Single-Cell Transcriptome Data

Cao

Zhengchao

et al. 2022

Front. Cardiovasc. Med.

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BackgroundVascular smooth muscle cell (VSMC) phenotype switching has been preliminarily found in aortic aneurysms. However, two major questions were raised: (1) What factors drive phenotypic switching of VSMCs in aortic aneurysms? (2) What role does VSMC phenotype transformation play in aortic aneurysms? We speculated that the interaction between infiltrated immune cells and VSMCs played a pivotal role in aortic aneurysm expansion.Materials and MethodsWe obtained single-cell transcriptome data GSE155468 that incorporate eight aortic aneurysm samples and three normal aorta samples. A standard single-cell analysis procedure was performed by Seurat (v3.1.2) for identifying the general cell components. Subsequently, VSMCs were extracted separately and re-clustered for identifying switched VSMC phenotypes. VSMC phenotype annotation was relied on the definitions of specific VSMC phenotypes in published articles. Vital VSMC phenotypes were validated by immunofluorescence. Next, identified immune cells and annotated vital VSMC phenotypes were extracted for analyzing the intercellular communication. R package CellChat (v1.1.3) was used for investigating the communication strength, signaling pathways, and communication patterns between various VSMC phenotypes and immune cells.ResultA total of 42,611 cells were identified as CD4 + T cells, CD8 + T cells, VSMC, monocytes, macrophages, fibroblasts, endothelial cells, and B cells. VSMCs were further classified into contractile VSMCs, secreting VSMCs, macrophage-like VSMCs, mesenchymal-like VSMCs, adipocyte-like VSMCs, and T-cell-like VSMCs. Intercellular communication analysis was performed between immune cells (macrophages, B cells, CD4 + T cells, CD8 + T cells) and immune related VSMCs (macrophage-like VSMCs, mesenchymal-like VSMCs, T-cell-like VSMCs, contractile VSMCs). Among selected cell populations, 27 significant signaling pathways with 61 ligand–receptor pairs were identified. Macrophages and macrophage-like VSMCs both assume the roles of a signaling sender and receiver, showing the highest communication capability. T cells acted more as senders, while B cells acted as receivers in the communication network. T-cell-like VSMCs and contractile VSMCs were used as senders, while mesenchymal-like VSMCs played a poor role in the communication network. Signaling macrophage migration inhibitory factor (MIF), galectin, and C-X-C motif chemokine ligand (CXCL) showed high information flow of intercellular communication, while signaling complement and chemerin were completely turned on in aortic aneurysms. MIF and galectin promoted VSMC switch into macrophage-like phenotypes, CXCL, and galectin promoted VSMCs transform into T-cell-like phenotypes. MIF, galectin, CXCL, complement, and chemerin all mediated the migration and recruitment of immune cells into aortic aneurysms.ConclusionThe sophisticated intercellular communication network existed between immune cells and immune-related VSMCs and changed as the aortic aneurysm progressed. Signaling MIF, galectin, CXCL, chemerin, and complement made a significant contribution to aortic aneurysm progression through activating immune cells and promoting immune cell migration, which could serve as the potential target for the treatment of aortic aneurysms.

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Section: Discussionmentioning

confidence: 99%

Deciphering the Intercellular Communication Between Immune Cells and Altered Vascular Smooth Muscle Cell Phenotypes in Aortic Aneurysm From Single-Cell Transcriptome Data

Cao

Zhengchao

et al. 2022

Front. Cardiovasc. Med.

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“…Interestingly, some authors state that chemerin participates in pre-eclampsia development by CMKLR1/Akt/enhancer-binding protein-alpha (CEBPα) axis activation and angiogenesis suppression and induces M1 macrophage polarization [ 152 ]. Expression levels of chemerin, pregnancy-associated plasma protein A (PAPP-A), ox-LDL, and matrix metalloproteinase 9 were found to be independent risk factors for neurological impairment in ischemic cerebrovascular disease patients [ 153 ].…”

Section: Chemerinmentioning

confidence: 99%

Role of Chemerin in Cardiovascular Diseases

et al. 2022

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(1) Background: Obesity is closely connected to the pathophysiology of cardiovascular diseases (CVDs). Excess fat accumulation is associated with metabolic malfunctions that disrupt cardiovascular homeostasis by activating inflammatory processes that recruit immune cells to the site of injury and reduce nitric oxide levels, resulting in increased blood pressure, endothelial cell migration, proliferation, and apoptosis. Adipose tissue produces adipokines, such as chemerin, that may alter immune responses, lipid metabolism, vascular homeostasis, and angiogenesis. (2) Methods: We performed PubMed and MEDLINE searches for articles with English abstracts published between 1997 (when the first report on chemerin identification was published) and 2022. The search retrieved original peer-reviewed articles analyzed in the context of the role of chemerin in CVDs, explicitly focusing on the most recent findings published in the past five years. (3) Results: This review summarizes up-to-date findings related to mechanisms of chemerin action, its role in the development and progression of CVDs, and novel strategies for developing chemerin-targeting therapeutic agents for treating CVDs. (4) Conclusions: Extensive evidence points to chemerin’s role in vascular inflammation, angiogenesis, and blood pressure modulation, which opens up exciting perspectives for developing chemerin-targeting therapeutic agents for the treatment of CVDs.

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“…Additionally, chemerin stimulated M1 macrophage polarization through the CMKLR1/Akt/CEBPα/IRF8 signaling axis, thus inhibiting macrophage-induced trophoblast invasion and migration as well as suppressing macrophage-mediated angiogenesis in vitro. When blockage of the chemerin/CMKLR1 axis by α-NETA occurs, M1 macrophage polarization and PE-like syndromes are both alleviated in a rat PE model [ 120 ]. Recently, a pregnant mouse model with trophoblastic-specific overexpression of chemerin was reported to manifest a PE-like phenotype (hypertension, proteinuria, and endotheliosis) accompanied by compromised trophoblast invasion, up-regulation of sFlt-1 (soluble Fms-like tyrosine kinase-1) and the inflammation markers as well as the poor pregnancy outcomes [ 119 ].…”

Section: Roles Of Chemerin System In Reproductive System Diseasesmentioning

confidence: 99%

Chemerin: A Functional Adipokine in Reproductive Health and Diseases

Yang

Huang

et al. 2022

Biomedicines

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As a multifaceted adipokine, chemerin has been found to perform functions vital for immunity, adiposity, and metabolism through its three known receptors (chemokine-like receptor 1, CMKLR1; G-protein-coupled receptor 1, GPR1; C-C motif chemokine receptor-like 2, CCRL2). Chemerin and the cognate receptors are also expressed in the hypothalamus, pituitary gland, testis, ovary, and placenta. Accumulating studies suggest that chemerin participates in normal reproduction and underlies the pathological mechanisms of certain reproductive system diseases, including polycystic ovary syndrome (PCOS), preeclampsia, and breast cancer. Herein, we present a comprehensive review of the roles of the chemerin system in multiple reproductive processes and human reproductive diseases, with a brief discussion and perspectives on future clinical applications.

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Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBPɑ axis and inducing M1 macrophage polarization

Cited by 25 publications

References 42 publications

Deciphering the Intercellular Communication Between Immune Cells and Altered Vascular Smooth Muscle Cell Phenotypes in Aortic Aneurysm From Single-Cell Transcriptome Data

Deciphering the Intercellular Communication Between Immune Cells and Altered Vascular Smooth Muscle Cell Phenotypes in Aortic Aneurysm From Single-Cell Transcriptome Data

Role of Chemerin in Cardiovascular Diseases

Chemerin: A Functional Adipokine in Reproductive Health and Diseases

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