The role of Chemerin in human diseases

Yue, Gengyu; An, Qimin; Xu, Xiaolin; Jin, Zhe; Ding, Jianhong; Hu, Yanxia; Du, Qian; Xu, Jie; Xie, Rui

doi:10.1016/j.cyto.2022.156089

Cited by 6 publications

(2 citation statements)

References 77 publications

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“…There is increasing awareness of the importance of chemerin in immune regulation and lipid biogenesis, that are biological processes associated with a number of common illnesses including acute inflammation, psoriasis, angiogenesis, obesity, diabetes, nonalcoholic fatty liver disease, ovarian cancer and endometrial cancer (Bozaoglu et al, 2007; Ernst & Sinal, 2010; Goralski et al, 2019; Goralski et al, 2007; Helfer & Wu, 2018; Kennedy & Davenport, 2018; Macvanin et al, 2022; Parolini et al, 2007; Schioppa et al, 2020; Su et al, 2021; Sun et al, 2021; Yue et al, 2023). It is therefore necessary to understand how chemerin exerts these physiological and pathological functions through the chemerin receptors.…”

Section: Discussionmentioning

confidence: 99%

Cryo-EM structures of the human G-protein coupled receptor 1 (GPR1) – Gi protein complexes bound to the full-length chemerin and to its C-terminal nonapeptide

Liu

Chen

et al. 2023

Preprint

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Chemerin is a chemoattractant and adipokine protein that acts on G protein-coupled receptors including chemokine-like receptor 1 (CMKLR1), G-protein coupled receptor 1 (GPR1) and C-C chemokine receptor-like 2 (CCRL2), mainly through its C-terminal peptide containing the sequence YFPGQFAFS (C-terminal nonapeptide or C9). Previous studies suggest that the three receptors respond to chemerin and C9 differently, with activation of the Gi signaling pathway through CMKLR1 but not GPR1 and CCRL2. Recently we reported a cryo-EM structure of human CMKLR1 in complex with Gi proteins and the C9 peptide. To identify structural differences among these receptors in ligand binding and Gi protein signaling, here we report a high-resolution cryo-EM structure of human GPR1-Gi complex bound to C9. Our structural and functional results show that GPR1 is able to respond to the C9 peptide with activation of the Gi signaling pathway and forms complex with a Gi protein. Similar to the CMKLR1-C9 structure, C9 adopts a C-terminus-in and S-shaped pose in the binding pocket. C9 is stabilized through hydrophobic interactions involving its Y1, F2, Q5, F6 and F8, and polar interactions between the P3, G4, Q5, F6, F8, S9 and residues lining the GPR1 binding pocket. An analysis of the GPR1-Gi protein interface found high similarities to the CMKLR1-Gi complex, and site-directed mutagenesis with functional verifications support GPR1 as a Gi-coupling receptors. These findings provide a structural basis of ligand recognition and Gi protein coupling by GPR1, and may help to understand the respective functions of the three chemerin receptors.

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Section: Discussionmentioning

confidence: 99%

Cryo-EM structures of the human G-protein coupled receptor 1 (GPR1) – Gi protein complexes bound to the full-length chemerin and to its C-terminal nonapeptide

Liu

Chen

et al. 2023

Preprint

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“…(Jacenik & Fichna, 2020), and its main functions were initially found in immune response, adipogenesis, as well as glucose and lipid metabolism (Jacenik & Fichna, 2020). Recently, Chemerin has been reported to be involved in the pathogenesis of inflammation and in a wide range of diseases, such as cancer, preeclampsia, and polycystic ovary syndrome (Luo et al, 2021; Quan et al, 2021; Treeck & Buechler, 2020; Yue et al, 2023). The serum contents of Chemerin are significantly elevated in various inflammatory diseases and contribute to the development of inflammation by aggregating different types of inflammatory cells (chemotaxis of dendritic cells and macrophages) at the site of inflammation (Su et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Chemerin and IL‐17 are potential predictors and Chemerin silencing alleviates inflammatory response and bone remodeling in chronic rhinosinusitis

Xie,

Bai,

Zhou

et al. 2023

Chem Biol Drug Des

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Chronic rhinosinusitis (CRS) is an inflammatory disease of paranasal sinuses. This study is formulated to explore the roles of pro‐inflammatory factors Chemerin and interleukin‐17 (IL‐17) in CRS. Patients suffering from CRS without/with nasal polyps (CRSsNP/CRSwNP), along with volunteers, were recruited. CRS rabbit models were constructed by Staphylococcus aureus infection and rabbits were injected with lentiviral vectors of short hairpin RNA‐targeting Chemerin (shChemerin), followed by micro‐computed tomography (CT) scan. Levels of Chemerin and IL‐17 were determined, and histopathological lesions were observed in subjects and CRS rabbits. Correlations between Chemerin/IL‐17 level and Lund‐Mackay/Lund‐Kennedy scores of subjects and the predictive value of Chemerin or IL‐17 for CRS were analyzed. In CRS patients and rabbits, inflammatory degrees and the level of Chemerin/IL‐17 were increased in pathological tissues or plasma, while Chemerin silencing alleviated CRS symptoms of CRS rabbits. Chemerin and IL‐17 were mainly located in the immune cells of pathological tissues and presented the positive correlation with Lund‐Mackay/Lund‐Kennedy score of CRS patients. Also, they showed high predictive value for CRS. Micro‐CT scan uncovered that CRS rabbits had increased bone remodeling, which was alleviated by Chemerin silencing. Collectively, Chemerin and IL‐17 are potential predictors and Chemerin silencing alleviates inflammatory response and bone remodeling in chronic rhinosinusitis.

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