SCARF1: a multifaceted, yet largely understudied, scavenger receptor

Patten, Daniel

doi:10.1007/s00011-018-1154-7

Cited by 36 publications

(41 citation statements)

References 47 publications

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“…97 In this study, SCARF1 contributed to the firm adhesion step of the leukocyte adhesion cascade, with endothelial surface expression of SCARF1 observed in adhesive cup structures formed on the surface of the LSEC. 97 However, SCARF1 is an understudied scavenger receptor 98 and more research into the extent of the contribution of SCARF1 in immune cell recruitment is required before it can be considered as a therapeutic target. Nevertheless, SRs including SCARF1 have been shown to be upregulated in several human inflammatory liver diseases and appear to accumulate at the interface between inflammation/fibrosis and correlate with fibrosis progression.…”

Section: Atypical Adhesion Moleculesmentioning

confidence: 99%

Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases

et al. 2019

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Immune dysregulation and accumulation of leukocytes is a hallmark of adult chronic liver diseases. Progressive hepatic inflammation can lead to fibrosis and cirrhosis with a high risk of liver failure or hepatocellular cancer (HCC). Recent advances have been made in the treatment of liver disease including the development of highly effective antiviral therapy for hepatitis C and the potential of immunotherapy for HCC. Despite this, the majority of other chronic liver diseases including alcoholic liver disease, fatty liver disease, and cholestatic diseases do not respond to conventional anti-inflammatory therapies. Recent studies defining the organ-specific properties that contribute to resident immune activation and immune cell recruitment from the circulation in these conditions have identified novel hepatic inflammatory pathways, which are now being targeted in clinical trials. Further understanding of how the immune microenvironment is regulated within the liver and how disease-specific mechanisms alter this process will hopefully lead to combination therapies to prevent aberrant inflammation and also promote fibrosis resolution. In this review, we focus on the advances that have been made in identifying key components of the inflammatory pathway including the recognition of danger signals, the recruitment and retention of lymphocytes from the circulation, and the pathways that promote resolution.

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Section: Atypical Adhesion Moleculesmentioning

confidence: 99%

Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases

et al. 2019

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“…Нокаут гена SR-F1 у мышей характеризуется тяжелым аутоиммунным фенотипом, напоминающим системную красную волчанку у человека [167]. Этот фенотип аутоиммунной болезни является следствием значительного ухудшения клиренса апоптозных клеток в органах иммунной системы.…”

Section: класс D представлен единственным рецептором Sr-d1 (Cd68)unclassified

“…Этот аутолиз был назван «вторичным некрозом» [232]. Он может быть связан с недостаточной активностью стромальных макрофагов в тканях на фоне большого числа апоптоза клеток [65,136] или дефицитом функции SR-F1 [167]. Вторичный некроз приводит к образованию DAMP и вовлекается в патогенез многих заболеваний, включая системную красную волчанку и болезнь Альцгеймера [191].…”

Section: класс D представлен единственным рецептором Sr-d1 (Cd68)unclassified

“…Кроме того, SR-F1 при связывании PAMP может образовывать комплексы с наружными видами TLR, ограничивая провоспалительные эффекты этих TLR [167].…”

Section: класс D представлен единственным рецептором Sr-d1 (Cd68)unclassified

“…Функция SR на начальной стадии развития тканевого стресса заключается в обеспечении питания делящихся клеток (холестерином, фосфолипидами, белками -источниками незаменимых аминокислот), в ограничении флогогенных механизмов клеточного стресса, а также в реализации адгезивной и миграционной активности клеток. Эти функции связаны со многими SR (глава 2), особенно: SR-B1 [5,149,152], SR-F1 [167], SR-F3 [101], SR-H1/2 [165,181,193,247], SR-I1 [9,51,190], SR-I2 [148], SR-K1 [198] [242]. Обозначенный уровень тканевого стресса также проявляет себя при развитии адаптивных физиологических процессов, связанных с кратковременным действием повреждающих факторов низкой интенсивности [83,146].…”

Section: Sr в обеспечении пролиферации клеток и тканевого ростаunclassified

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Physiological and pathogenic role of scavenger receptors in humans

et al. 2020

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The scavenger receptors (SRs)) include > 30 different molecules structurally classified into 11 classes (A to L). They are expressed mostly on stromal macrophages, and their expression may be augmented in direct dependence with concentrations of their ligands. The SRs are heterogenous by their structure, however, being common in their functional potential. E.g., different SR classes may participate in absorption of modified low-density lipoproteins and glycated proteins, apoptotic and ageing cells, altered erythrocytes and platelets, like as a big variety of other endogenous ligands from metabolic and cellular “trash”. A common property of SRs is their participation in removal of small pathogen amounts from blood circulation, regulation of cell and tissue stress responses, ability to form complicated receptor complexes with other receptor types including integrins and toll-like receptors. Opposite to classic pattern-recognizing receptors, the SR involvement does not always elicit a pronounced cellular activation and development of pro-inflammatory cellular stress. The SR functional effects provide interactions between different physiological events and immune system, including the processes of neuroendocrine and metabolic regulation. These mechanisms provide both homeostatic stability and, likewise, act at the border of normal and pathological conditions, i.e., participating in pathogenesis of transitional processes, e.g., physiological ageing. Moreover, the SR-associated processes represent a key pathogenetic factor in different somatic diseases, e.g., those associated with low-intensity chronic inflammation, including obesity, type 2 diabetes, atherosclerosis, arterial hypertension, various neurodegenerative disorders. Similarly, the SRs are involved into the processes of cancer transformation and antitumor response, different processes of classical inflammation, from antigen presentation to the morphofunctional T cell and macrophage polarization in the inflammation foci and immunocompetent organs. SR are playing a controversial role in development of acute systemic inflammation, the main reason for lethal outcomes in the intensive care wards. Targeted effects upon the SRs represent a promising approach when treating a broad variety of diseases, whereas detection of membrane-bound and soluble SR forms could be performed by means of diagnostic and monitoring techniques in many human disorders.

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Burden of Rare Genetic Variants in Spontaneous Coronary Artery Dissection With High-risk Features

et al. 2022

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ImportanceThe emerging genetic basis of spontaneous coronary artery dissection (SCAD) has been defined as both partially complex and monogenic in some patients, involving variants predominantly in genes known to underlie vascular connective tissue diseases (CTDs). The effect of these genetic influences has not been defined in high-risk SCAD phenotypes, and the identification of a high-risk subgroup of individuals may help to guide clinical genetic evaluations of SCAD.ObjectiveTo identify and quantify the burden of rare genetic variation in individuals with SCAD with high-risk clinical features.Design, Setting, and ParticipantsWhole-exome sequencing (WES) was performed for subsequent case-control association analyses and individual variant annotation among individuals with high-risk SCAD. Genetic variants were annotated for pathogenicity by in-silico analysis of genes previously defined by sequencing for vascular CTDs and/or SCAD, as well as genes prioritized by genome-wide association study (GWAS) and colocalization of arterial expression quantitative trait loci. Unbiased genome-wide association analysis of the WES data was performed by comparing aggregated variants in individuals with SCAD to healthy matched controls or the Genome Aggregation Database (gnomAD). This study was conducted at a tertiary care center. Individuals in the Canadian SCAD Registry genetics study with a high-risk SCAD phenotype were selected and defined as peripartum SCAD, recurrent SCAD, or SCAD in an individual with family history of arteriopathy.Main Outcomes and MeasuresBurden of genetic variants defined by DNA sequencing in individuals with high-risk SCAD.ResultsThis study included a total of 336 participants (mean [SD] age, 53.0 [9.5] years; 301 female participants [90%]). Variants in vascular CTD genes were identified in 17.0% of individuals (16 of 94) with high-risk SCAD and were enriched (OR, 2.6; 95% CI, 1.6-4.2; P = 7.8 × 10−4) as compared with gnomAD, with leading significant signals in COL3A1 (OR, 13.4; 95% CI, 4.9-36.2; P = 2.8 × 10−4) and Loeys-Dietz syndrome genes (OR, 7.9; 95% CI, 2.9-21.2; P = 2.0 × 10−3). Variants in GWAS-prioritized genes, observed in 6.4% of individuals (6 of 94) with high-risk SCAD, were also enriched (OR, 3.6; 95% CI, 1.6-8.2; P = 7.4 × 10−3). Variants annotated as likely pathogenic or pathogenic occurred in 4 individuals, in the COL3A1, TGFBR2, and ADAMTSL4 genes. Genome-wide aggregated variant testing identified novel associations with peripartum SCAD.Conclusions and RelevanceIn this genetic study, approximately 1 in 5 individuals with a high-risk SCAD phenotype harbored a rare genetic variant in genes currently implicated for SCAD. Genetic screening in this subgroup of individuals presenting with SCAD may be considered.

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SCARF1: a multifaceted, yet largely understudied, scavenger receptor

Cited by 36 publications

References 47 publications

Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases

Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases

Physiological and pathogenic role of scavenger receptors in humans

Burden of Rare Genetic Variants in Spontaneous Coronary Artery Dissection With High-risk Features

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