Prosaposin mediates inflammation in atherosclerosis

Leent, Mandy M. T. van; Beldman, Thijs J.; Toner, Yohana C.; Lameijer, Marnix; Rother, Nils; Bekkering, Siroon; Teunissen, Abraham J. P.; Zhou, Xianxiao; Meel, Roy van der; Malkus, Joost; Nauta, Sheqouia A.; Klein, Emma D.; Fay, François; Sánchez-Gaytán, Brenda L.; Pérez-Medina, Carlos; Kluza, Ewelina; Ye, Yuxiang; Wojtkiewicz, Gregory R.; Fisher, Edward A.; Świrski, Filip K.; Nahrendorf, Matthias; Zhang, Bin; Li, Yang; Zhang, Bowen; Joosten, Leo A. B.; Pasterkamp, Gérard; Boltjes, Arjan; Fayad, Zahi A.; Lutgens, Esther; Netea, Mihai G.; Riksen, Niels P.; Mulder, Willem J. M.; Duivenvoorden, Raphaël

doi:10.1126/scitranslmed.abe1433

Cited by 61 publications

(43 citation statements)

References 77 publications

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“…Atherosclerosis (AS) is closely related to inflammation and the disorder of lipid metabolism (Feng et al, 2020;van Leent et al, 2021). Inflammation promotes the change of endothelial cell function Wang et al (2013), which results in the release of pro-inflammatory factors, as well as the monocyte chemokines.…”

Section: Introductionmentioning

confidence: 99%

Catalpol Inhibits Macrophage Polarization and Prevents Postmenopausal Atherosclerosis Through Regulating Estrogen Receptor Alpha

Chen

Zhang

et al. 2021

Front. Pharmacol.

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Lacking estrogen increases the risk of atherosclerosis (AS) in postmenopausal women. Inflammation plays a vital role in the pathological process of AS, and macrophages are closely related to inflammation. Catalpol is an iridoid glucoside extracted from the fresh roots of the traditional Chinese herb Rehmanniae radix preparata. In this study, we aimed to evaluate the effects of catalpol on macrophage polarization and postmenopausal AS. In addition, we investigated whether the mechanism of catalpol was dependent on regulating the expression of estrogen receptors (ERs). In vitro, lipopolysaccharides (LPS) and interferon-γ (IFN-γ) were applied to induce M1 macrophage polarization. In vivo, the ApoE−/− mice were fed with a high-fat diet to induce AS, and ovariectomy was operated to mimic the estrogen cessation. We demonstrated catalpol inhibited M1 macrophage polarization induced by LPS and INF-γ, and eliminated lipid accumulation in postmenopausal AS mice. Catalpol not only suppressed the inflammatory response but also reduced the level of oxidative stress. Then, ERs (ERα and ERβ) inhibitors and ERα siRNA were also applied in confirming that the protective effect of catalpol was mediated by ERα, rather than ERβ. In conclusion, catalpol significantly inhibited macrophage polarization and prevented postmenopausal AS by increasing ERα expression.

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Section: Introductionmentioning

confidence: 99%

Catalpol Inhibits Macrophage Polarization and Prevents Postmenopausal Atherosclerosis Through Regulating Estrogen Receptor Alpha

Chen

Zhang

et al. 2021

Front. Pharmacol.

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“…Prosaposin (gene name PSAP) can be secreted from various cell types in response to cellular stress. Secreted PSAP can initiate endocytose or pro-survival signaling pathways via binding to GPR37 and GPR37L1 ( 88, 89 ). ST maps showed PSAP was enriched in scar-resident fibroblasts (data not shown) and GPR37L1 was enriched in scar-resident microglia (figure 5L), but the exact role of fibroblast secreted PSAP s should be explored in future.…”

Section: Resultsmentioning

confidence: 99%

Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury

Gong

Han

et al. 2021

Preprint

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Adult regeneration in spinal cord is poor in mammalian but remarkable in the neonatal mammals and some vertebrates, including fish and salamanders. Increasing evidences basis of this interspecies and ontogeny highlighted the pivotal roles of neuron extrinsic factors-the glial scar, which exert confusing inhibiting or promoting regeneration function, but the spatiotemporal ordering of cellular and molecular events that drive repair processes in scar formation remains poorly understood. Here, we firstly constructed tissue-wide gene expression measurements of mouse spinal cords over the course of scar formation using the spatial transcriptomics (ST) technology in Spinal cord injury (SCI) repair. We analyzed the transcriptomes of nearly 15449 spots from 32 samples and distinguished normal and damage response regions. Compared to histological changes, spatial mapping of differentiation transitions in spinal cord injury site delineated the possible trajectory between subpopulations of fibroblast, glia and immune cell more comprehensively and defined the extent of scar boundary and core more accurately. Locally, we identified gene expression gradients from leading edge to the core of scar areas that allow for re-understanding of the scar microenvironment and found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophage, CD36 and Postn in fibroblast, Plxnb2 and Nxpe3 in microglia, Clu in astrocyte and CD74 in oligodendrocyte. Last, we profiled the bidirectional ligand-receptor interactions at the neighbor cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found GPR37L1_PSAP and GPR37_PSAP were top 2 enriched gene-pairs between microglia and fibroblast or microglia and astrocyte. Together, the establishment of these profiles firstly uncovered scar spatial heterogeneity and lineage trajectory, provide an unbiased view of scar and served as a valuable resource for CNS injury treatment.

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“…Prosaposin (gene name PSAP) can be secreted from various cell types in response to cellular stress. Secreted PSAP can initiate endocytose or pro-survival signaling pathways via binding to GPR37 and GPR37L1 (91,92). ST maps showed PSAP was enriched in scar-resident broblasts (data not shown) and GPR37L1 was enriched in scar-resident microglia ( gure 5L), but the exact role of broblast secreted PSAP s should be explored in future.…”

Section: St Analysis Of Microglia Heterogeneity Reveals the Speci C Roles During Gliosismentioning

confidence: 96%

Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury

Zhou¹,

Gong

Gu³

et al. 2022

Preprint

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Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors-the glial scar, triggered by injury and exerting confusing inhibiting or promoting regeneration function. Recent technological advancements in spatial transcriptomics (ST) provide a unique opportunity to decipher all or most genes systematically throughout scar formation, which remains poorly understood. Herein, we firstly constructed tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury (SCI) based on the transcriptomes from 32 samples. Locally, we identified gene expression gradients from leading edge to the core of scar areas that allow for re-understanding of the scar microenvironment, such as neurotransmitter disorder, activation of proinflammatory response, neurotoxic saturated lipids, angiogenesis, obstructing axon extension and extracellular structure re-organization. Additionally, we identified 21 cell types during scar formation and delineated the origin, functional diversity and the possible trajectory between subpopulations of fibroblast, glia and immune cell. Specially, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophage, CD36 and Postn in fibroblast, Plxnb2 and Nxpe3 in microglia, Clu in astrocyte and CD74 in oligodendrocyte. Subsequently, we accurately defined the extent of scar boundary and profiled the bidirectional ligand-receptor interactions at the neighbor cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found GPR37L1_PSAP and GPR37_PSAP were the most significant gene-pairs between microglia, fibroblasts and astrocytes. Last, we quantified the fraction of scar-resident cell and defined four phases of the scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence and scar stationary. Together, the establishment of these profiles firstly uncovered scar spatial heterogeneity and lineage trajectory, provide an unbiased view of scar and served as a valuable resource for the central nervous system (CNS) injury treatment.

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Prosaposin mediates inflammation in atherosclerosis

Cited by 61 publications

References 77 publications

Catalpol Inhibits Macrophage Polarization and Prevents Postmenopausal Atherosclerosis Through Regulating Estrogen Receptor Alpha

Catalpol Inhibits Macrophage Polarization and Prevents Postmenopausal Atherosclerosis Through Regulating Estrogen Receptor Alpha

Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury

Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury

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