Osteopontin promotes age-related adipose tissue remodeling through senescence-associated macrophage dysfunction

Sawaki, Daigo; Zhang, Yanyan; Mohamadi, Amel; Pini, Maria Silvia; Mezdari, Zaineb; Lipskaia, Larissa; Naushad, Suzain; Lamendour, Lucille; Altintas, Dogus Murat; Bréau, Marielle; Liang, Hao; Halfaoui, Maissa; Delmont, Thaïs; Surénaud, Mathieu; Rousseau, Denis; Yoshimitsu, Takehiko; Louache, Fawzia; Adnot, Serge; Hénégar, Corneliu; Gual, Philippe; Czibik, Gabor; Dérumeaux, Geneviève

doi:10.1172/jci.insight.145811

Cited by 13 publications

(8 citation statements)

References 49 publications

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“…Among them, SPP1 showed the best predictive value. SPP1, also known as osteopontin, is involved in a variety of physiological and pathological processes including wound healing, bone turnover, tumorigenesis, inflammation, ischemia, and immune responses [ 46 , 47 ]. SPP1 is expressed by a variety of inflammatory cells in culture, including T cells, macrophages, and NK cells [ 48 – 50 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis

Qiu,

Feng,

Liu

et al. 2024

Arthritis Res Ther

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Background Anti-melanoma differentiation-associated gene five antibody positive (MDA5+) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate prognostic factors for RP-ILD in MDA5+ DM patients. Methods Plasma samples from 20 MDA5+ DM patients and 10 healthy controls (HC) were collected for proteomic analysis using liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis. The proteins of interest were validated in independent samples (20 HC, 20 MDA5+ DM with RP-ILD, and 20 non-RP-ILD patients) with enzyme-linked immunosorbent assay (ELISA). Results A total of 413 differentially expressed proteins (DEPs) were detected between the MDA5+ DM patients and HC. When comparing DEPs between RP-ILD and non-RP-ILD patients, 79 proteins were changed in RP-ILD patients, implicating acute inflammatory response, coagulation, and complement cascades. Six candidate biomarkers were confirmed with ELISA. Secreted phosphoprotein 1 (SPP1), serum amyloid A1 (SAA1), and Kininogen 1 (KNG1) concentrations were significantly elevated in RP-ILD patients than those in non-RP-ILD patients and HC. In the different clinical subgroups, SPP1 was particularly elevated in the high-risk RP-ILD subgroup of MDA5+ DM. Conclusion This study provides novel insights into the pathogenesis of RP-ILD development in MDA5+ DM and suggests the plasma protein SPP1 could serve as a potential blood biomarker for RP-ILD early warning.

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Section: Discussionmentioning

confidence: 99%

Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis

Qiu,

Feng,

Liu

et al. 2024

Arthritis Res Ther

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“…In contrast to CCL2, OPN may not directly influence macrophage polarization, as subtypes of adipose tissue macrophages and BMDM are not altered in mice deficient for Spp1 (Schuch et al., 2016 ). However, OPN has been shown to induce a senescence‐like phenotype in adipose tissue macrophages through CD44, evidenced by increased p16 , senescence‐associated B‐galactosidase activity, proinflammatory and profibrotic behavior, and impaired efferocytosis (Sawaki et al., 2023 ). Of note, Spp1 is also highly expressed in dystrophic skeletal muscle, and constitutive deletion of Spp1 in the mdx mouse attenuates immune cell infiltration and fibrosis (Capote et al., 2016 ; Vetrone et al., 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Senescent skeletal muscle fibroadipogenic progenitors recruit and promote M2 polarization of macrophages

Zhang,

Ng,

Chini

et al. 2023

Aging Cell

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Senescent cells compromise tissue structure and function in older organisms. We recently identified senescent fibroadipogenic progenitors (FAPs) with activated chemokine signaling pathways in the skeletal muscle of old mice, and hypothesized these cells may contribute to the age‐associated accumulation of immune cells in skeletal muscle. In this study, through cell–cell communication analysis of skeletal muscle single‐cell RNA‐sequencing data, we identified unique interactions between senescent FAPs and macrophages, including those mediated by Ccl2 and Spp1. Using mouse primary FAPs in vitro, we verified increased expression of Ccl2 and Spp1 and secretion of their respective proteins in the context of both irradiation‐ and etoposide‐induced senescence. Compared to non‐senescent FAPs, the medium of senescent FAPs markedly increased the recruitment of macrophages in an in vitro migration assay, an effect that was mitigated by preincubation with antibodies to either CCL2 or osteopontin (encoded by Spp1). Further studies demonstrated that the secretome of senescent FAPs promotes polarization of macrophages toward an M2 subtype. These data suggest the unique secretome of senescent FAPs may compromise skeletal muscle homeostasis by recruiting and directing the behavior of macrophages.

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“…The aging of the immune system is one of the causes of inflammaging, and innate immune cells drive inflammaging by increasing pro-inflammatory subpopulations and generating pro-inflammatory responses ( 17 ). And, macrophages, which are important players in immune surveillance and clearance of aging cells during immunosenescence, are highly susceptible to aging ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatic analysis and experimental validation for exploring the key molecular of brain inflammaging

Wang

Yang

et al. 2023

Front. Immunol.

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AimsIntegrating bioinformatics and experimental validation to explore the mechanisms of inflammaging in the Brain.MethodAfter dividing the GSE11882 dataset into aged and young groups, we identified co-expressed differentially expressed genes (DEGs) in different brain regions. Enrichment analysis revealed that the co-expressed DEGs were mainly associated with inflammatory responses. Subsequently, we identified 12 DEGs that were related to the inflammatory response and used the DGIdb website for drug prediction. By using both the least absolute shrinkage and selection operator (LASSO) and random forest (RF), four biomarkers were screened and an artificial neural network (ANN) was developed for diagnosis. Subsequently, the biomarkers were validated through animal studies. Then we utilized AgeAnno to investigate the roles of biomarkers at the single cell level. Next, a consensus clustering approach was used to classify the aging samples and perform differential analysis to identify inflammatory response-related genes. After conducting a weighted gene co-expression network analysis (WGCNA), we identified the genes that are correlated with both four brain regions and aging. Wayne diagrams were used to identify seven inflammaging-related genes in different brain regions. Finally, we performed immuno-infiltration analysis and identified macrophage module genes.Key findingsInflammaging may be a major mechanism of brain aging, and the regulation of macrophages by CX3CL1 may play a role in the development of inflammaging.SignificanceIn summary, targeting CX3CL1 can potentially delay inflammaging and immunosenescence in the brain.

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Osteopontin promotes age-related adipose tissue remodeling through senescence-associated macrophage dysfunction

Cited by 13 publications

References 49 publications

Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis

Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis

Senescent skeletal muscle fibroadipogenic progenitors recruit and promote M2 polarization of macrophages

Integrated bioinformatic analysis and experimental validation for exploring the key molecular of brain inflammaging

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