Peishen Zhao

FPR1-Driven Neutrophil-Endothelial Cell Axis Promotes Angiogenesis in PAOD

Fengyang Li, Peishen Zhao, Tianshu Wei, Yuqin Zha et autres

BACKGROUND: Peripheral artery occlusive disease (PAOD) is characterized by limb ischemia, heightened inflammation, and a substantial risk of mortality and amputation. Coordinated regulation of inflammation resolution and angiogenesis represents a promising therapeutic strategy. Given the established roles of FPRs (formyl peptide receptors) …

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Therapeutic effects of a dual formylpeptide receptor agonist in pulmonary arterial hypertension mouse model

Ting Fu, Chloe Landy, Miles J. De Blasio, Jaideep Singh et autres

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Global Sirt5 deletion reshapes gut microbiota and impairs glucose metabolism in high-fat diet-induced obese mice

Hui Cao, Xu Kejia, Xiaojue Li, Quan Liu et autres

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Structural basis of modified ligand selectivity from N-terminal PAC1R alternative splicing

Jessica Bo Li Lu, Giuseppe Deganutti, Miaomiao Li, Laura J. Humphrys et autres

The pituitary adenylate cyclase-activating polypeptide (PACAP) 1 receptor (PAC1R) is a class B1 G protein–coupled receptor activated by the endogenous peptide agonists PACAP and vasoactive intestinal peptide (VIP). Alternate splicing within the receptor extracellular domain (ECD) generates the PAC1R short variant (PAC1sR) …

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Formylpeptide receptors: A novel target to treat cardiometabolic complications

Chen Huei Leo, Elizabeth A. Vecchio, Ting Fu, Xiangyan Yi et autres

The formylpeptide receptor (FPR) family, particularly FPR2, has emerged as a master regulator of inflammation and its resolution. Given that both cardiovascular diseases and metabolic disorders are characterised by pro-inflammatory scenarios, often with resultant impairment of the healing response to (i.e. resolution …

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Contrasting roles for GLP-1R and GIPR in a model of diet-induced obesity

Jie Gao, Shelby Cree, Seungmin Ham, Cameron J. Nowell et autres

The glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are important incretin receptors that are therapeutic targets for the treatment of type 2 diabetes and obesity. This study extensively characterised the metabolic phenotype of mice with global deletion of either …

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FPR2 Agonism Attenuates Restenosis by Mitigating Neointimal Hyperplasia via ELOVL6

Yukun Zha, Xiaoting Wang, Peishen Zhao, Owen L. Woodman et autres

Restenosis following endovascular intervention in lower extremity arterial disease contributes to significant morbidity and mortality. This study investigates the role of formylpeptide receptor 2 (FPR2) in neointimal hyperplasia and evaluates the therapeutic potential of the selective FPR2 agonist BMS-986235 in mitigating restenosis. …

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Unique Biased Agonism Profile of βCGRP on CGRP Family Receptors

Grace Mennen, Madeleine M. Fletcher, Muhammad Abdur Razzak, Laura J. Humphrys et autres

α- and β-calcitonin gene-related peptides (αCGRP and βCGRP, respectively), together with adrenomedullin (AM) and AM2 are endogenous agonists of the CGRP family of receptors; CGRP receptor (CGRPR), AM 1 receptor (AM 1 R), and AM 2 receptor (AM 2 R). The high …

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Lipoxin A4 improves cardiac remodeling and function in diabetes-associated cardiac dysfunction

Ting Fu, Muthukumar Mohan, Madhura Bose, Eoin Patrick Brennan et autres

Abstract Background Diabetic heart disease may eventually lead to heart failure, a leading cause of mortality in diabetic individuals. The lack of effective treatments for diabetes-induced heart failure may result from a failure to address the underlying pathological processes, including chronic, low-grade …

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Biased receptor signalling and intracellular trafficking profiles of structurally distinct formylpeptide receptor 2 agonists

Cheng Peng, Elizabeth A. Vecchio, Thi Nguyen, Mia De Seram et autres

BACKGROUND: There is increasing interest in developing FPR2 agonists (compound 43, ACT-389949 and BMS-986235) as potential pro-resolving therapeutics, with ACT-389949 and BMS-986235 having entered phase I clinical development. FPR2 activation leads to diverse downstream outputs. ACT-389949 was observed to cause rapid tachyphylaxis, …

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Cholesterol-dependent dynamic changes in the conformation of the type 1 cholecystokinin receptor affect ligand binding and G protein coupling

Kaleeckal G. Harikumar, Peishen Zhao, Brian P. Cary, Xiaomeng Xu et autres

Development of optimal therapeutics for disease states that can be associated with increased membrane cholesterol requires better molecular understanding of lipid modulation of the drug target. Type 1 cholecystokinin receptor (CCK1R) agonist actions are affected by increased membrane cholesterol, enhancing ligand binding …

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The involvement of the Wnt/β-catenin signaling cascade in fibrosis progression and its therapeutic targeting by relaxin

Deidree V. N. Somanader, Peishen Zhao, Robert E. Widdop, Chrishan S. Samuel

Organ scarring, referred to as fibrosis, results from a failed wound-healing response to chronic tissue injury and is characterised by the aberrant accumulation of various extracellular matrix (ECM) components. Once established, fibrosis is recognised as a hallmark of stiffened and dysfunctional tissues, …

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