Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS)

Lin, Elliot Yi-Hsin; Xi, Wen; Aggarwal, Nupur; Shinohara, Mari L.

doi:10.1093/intimm/dxac060

Cited by 19 publications

(20 citation statements)

References 110 publications

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“…Spp1 is a multifunctional protein involved in various biological processes, including cell adhesion, migration, immune regulation, and the in ammation cascade [12] . In the eld of cardiovascular research, the role of Spp1 is increasingly recognized due to its association with the onset and progression of various cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals That Ccr2+ Macrophages Can Promote Myocardial Fibrosis After Myocardial Ischemia-Reperfusion Injury by Recruiting Fibroblasts

Lou,

Liao,

Liu

et al. 2024

Preprint

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Coronary reperfusion following myocardial ischemia can lead to myocardial ischemia-reperfusion injury (MIRI).Ccr2 + macrophages play a pivotal role in MIRI, engaging not only in acute inflammatory responses but also in the formation of cardiac fibrosis. The mechanisms underlying the latter are not yet fully elucidated.This study aims to explore the mechanism by which this macrophage subgroup promotes myocardial fibrosis after MIRI through bioinformatics analysis of Ccr2 + macrophages in MIRI, and to identify more molecular markers for this subgroup in MIRI. We sourced scRNA-seq and bulk RNA-seq data corresponding to mice models of MIRI from the GEO database and executed detailed bioinformatics analyses.The results revealed that after MIRI, Ccr2 + macrophages underwent M2 phenotype polarization and engaged in extensive signal interactions with fibroblasts and immune cells via the Spp1 signaling pathway. Spp1, likely by binding to the integrin receptors of fibroblasts, activates the PI3K-Akt pathway, whose activation can promote the adhesion and migration of fibroblasts, thereby facilitating myocardial fibrosis. Furthermore, we identified Spp1 as a molecular marker for Ccr2 + macrophages in MIRI and externally validated the tissue-level differences of Spp1 through additional bulk RNAseq. This study provides potential therapeutic targets for acute inflammation and chronic myocardial fibrosis occurring after MIRI.

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Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals That Ccr2+ Macrophages Can Promote Myocardial Fibrosis After Myocardial Ischemia-Reperfusion Injury by Recruiting Fibroblasts

Lou,

Liao,

Liu

et al. 2024

Preprint

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“…At P5, but not P6, CCL2 transcript levels were highly increased by ethanol. SPP1, which is also termed osteopontin, is a secretory molecule expressed by a variety of immune cells which has functions including immunomodulation, chemotaxis, and cell adhesion ( Lin et al, 2022 ). SPP1 plays a role in alcohol liver disease ( Apte et al, 2005 ; Seth et al, 2006 ; Lebel et al, 2008 ; Das et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Ethanol-induced cerebellar transcriptomic changes in a postnatal model of fetal alcohol spectrum disorders: Focus on disease onset

et al. 2023

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Fetal alcohol spectrum disorders (FASD) are a group of neurodevelopmental disorders caused by ethanol exposure in utero, which can result in neurocognitive and behavioral impairments, growth defects, and craniofacial anomalies. FASD affects up to 1-5% of school-aged children in the United States, and there is currently no cure. The underlying mechanisms involved in ethanol teratogenesis remain elusive and need greater understanding to develop and implement effective therapies. Using a third trimester human equivalent postnatal mouse model of FASD, we evaluate the transcriptomic changes induced by ethanol exposure in the cerebellum on P5 and P6, after only 1 or 2 days of ethanol exposure, with the goal of shedding light on the transcriptomic changes induced early during the onset and development of FASD. We have highlighted key pathways and cellular functions altered by ethanol exposure, which include pathways related to immune function and cytokine signaling as well as the cell cycle. Additionally, we found that ethanol exposure resulted in an increase in transcripts associated with a neurodegenerative microglia phenotype, and acute- and pan-injury reactive astrocyte phenotypes. Mixed effects on oligodendrocyte lineage cell associated transcripts and cell cycle associated transcripts were observed. These studies help to elucidate the underlying mechanisms that may be involved with the onset of FASD and provide further insights that may aid in identifying novel targets for interventions and therapeutics.

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“…The cDNA was a murine homologue of rat bone OPN identified three years earlier [3]. It has been known for a long time that OPN is involved in immune processes and expressed by many different types of immune cells [111]. The concentration of OPN in milk is orders of magnitude higher than anywhere else in the body, which could indicate that OPN plays a role either as part of the innate immune system in milk, or as a modulator of immune responses in neonates and infants.…”

Section: Milk Osteopontin and Immunological Effectsmentioning

confidence: 99%

Milk Osteopontin and Human Health

Sørensen

Christensen

2023

Nutrients

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Osteopontin (OPN) is a multifunctional protein found in all vertebrates. OPN is expressed in many different cell types, and is consequently found in most tissues and physiological secretions. OPN is involved in a multitude of biological processes, such as activation and regulation of the immune system; biomineralization; tissue-transformative processes, including growth and development of the gut and brain; interaction with bacteria; and many more. OPN is found in the highest concentrations in milk, where it is believed to initiate and regulate developmental, immunological and physiological processes in infants who consume milk. Processes for the isolation of bovine OPN for use in infant formula have been developed, and in recent years, many studies have investigated the effects of the intake of milk OPN. The purpose of this article is to review and compare existing knowledge about the structure and function of milk OPN, with a particular focus on the effects of milk OPN on human health and disease.

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Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS)

Cited by 19 publications

References 110 publications

Single-Cell RNA Sequencing Reveals That Ccr2+ Macrophages Can Promote Myocardial Fibrosis After Myocardial Ischemia-Reperfusion Injury by Recruiting Fibroblasts

Single-Cell RNA Sequencing Reveals That Ccr2+ Macrophages Can Promote Myocardial Fibrosis After Myocardial Ischemia-Reperfusion Injury by Recruiting Fibroblasts

Ethanol-induced cerebellar transcriptomic changes in a postnatal model of fetal alcohol spectrum disorders: Focus on disease onset

Milk Osteopontin and Human Health

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