Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants

Gravina, Giacomo; Ardalan, Maryam; Chumak, Tetyana; Nilsson, Anders; Ek, Joakim; Danielsson, Hanna; Svedin, Pernilla; Pekny, Milos; Pekna, Marcela; Sävman, Karin; Hellström, Ann; Mallard, Carina

doi:10.1016/j.isci.2023.107217

Cited by 5 publications

(1 citation statement)

References 69 publications

(86 reference statements)

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“…SAT samples were prepared as in ref. 77 . Aliquots (30 µg) were trypsin digested using the modified filter-aided sample preparation method ( 78 ).…”

Section: Methodsmentioning

confidence: 99%

A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice

Vujičić,

Broderick,

Salmantabar

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Efficient removal of fibrillar collagen is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we used mice to further define the mechanism for this collagenolytic process. We show that loss of collagen type-1 (CT1) and increased CT1-fragment levels in expanding SAT are associated with proliferation of resident M2-like macrophages that display increased CD206-mediated engagement in collagen endocytosis compared to chow-fed controls. Blockage of CD206 during acute high-fat diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, these SAT macrophages’ engagement in collagen endocytosis is diminished in obesity associated with elevated levels collagen fragments that are too short to assemble into triple helices. We show that such short fragments provoke M2-macrophage proliferation and fibroinflammatory changes in fibroblasts. In conclusion, our data delineate the importance of a macrophage-collagen fragment axis in physiological SAT expansion. Therapeutic targeting of this process may be a means to prevent pathological adipose tissue remodeling, which in turn may reduce the risk for obesity-related metabolic disorders.

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“…SAT samples were prepared as in ref. 77 . Aliquots (30 µg) were trypsin digested using the modified filter-aided sample preparation method ( 78 ).…”

Section: Methodsmentioning

confidence: 99%

A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice

Vujičić,

Broderick,

Salmantabar

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Maternal obesity alters fetal neuroinflammation in a murine model of preterm birth

Leonard,

Schmiedecke,

Talley

et al. 2024

AJOG Global Reports

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Lipocalin-2 as a mediator of neuroimmune communication

Afridi,

Kim,

Bhusal

et al. 2023

Journal of Leukocyte Biology

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Lipocalin-2 (LCN2), a neutrophil gelatinase-associated lipocalin (NGAL), is a 25 kDa secreted protein implicated in a broad range of inflammatory diseases affecting the brain and periphery. It is a pleotropic protein expressed by various immune and non-immune cells throughout the body. Importantly, the surge in LCN2 levels in disease states has been associated with a myriad of undesirable effects, further exacerbating the ongoing pathological processes. In the brain, glial cells are the principal source of LCN2, which plays a definitive role in determining their functional phenotypes. In different central nervous system (CNS) pathologies, an increased expression of glial LCN2 has been linked to neurotoxicity. LCN2 mediates a crosstalk between central and peripheral immune cells under neuroinflammatory conditions. One intriguing aspect is that elevated LCN2 levels in peripheral disorders, such as cancer, metabolic conditions, and liver diseases, potentially incite an inflammatory activation of glial cells while disrupting neuronal functions. This review comprehensively summarizes the influence of LCN2 on the exacerbation of neuroinflammation by regulating various cellular processes. Additionally, this review explores LCN2 as a mediator of neuroimmune crosstalk in various CNS pathologies and highlights the role of LCN2 in carrying inflammatory signals along the neuroimmune axis.

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Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants

Cited by 5 publications

References 69 publications

A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice

A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice

Maternal obesity alters fetal neuroinflammation in a murine model of preterm birth

Lipocalin-2 as a mediator of neuroimmune communication

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