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Resolvin D2-GPR18 Enhances Bone Marrow Function and Limits Steatosis and Hepatic Collagen Accumulation in Aging

ABSTRACT: Resolvin D2-GPR18 Enhances Bone Marrow Function and Limits Steatosis and Hepatic Collagen Accumulation in Aging

PROVIDER: PRJNA993234 | ENA |

REPOSITORIES: ENA

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Resolvin D2-GPR18 Enhances Bone Marrow Function and Limits Steatosis and Hepatic Collagen Accumulation in Aging

Project description:Aging is associated with nonresolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a proresolving ligand that acts through the G-protein-coupled receptor called GPR18. Unbiased RNA sequencing revealed increased Gpr18 expression in macrophages from old mice, and in livers from elderly humans, which was associated with increased steatosis and fibrosis in middle-aged (MA) and old mice. MA mice that lack GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages. Treatment of MA mice with RvD2 reduced steatosis and decreased hepatic fibrosis, correlating with increased Mac2+ macrophages, increased monocyte-derived macrophages, and elevated numbers of monocytes in the liver, blood, and bone marrow. RvD2 acted directly on the bone marrow to increase monocyte-macrophage progenitors. A transplantation assay further demonstrated that bone marrow from old mice facilitated hepatic collagen accumulation in young mice, and transient RvD2 treatment to mice transplanted with bone marrow from old mice prevented hepatic collagen accumulation. Together, this study demonstrates that RvD2-GPR18 signaling controls steatosis and fibrosis and provides a mechanistic-based therapy for promoting liver repair in aging.

2023-08-08 | GSE236974 | GEO

Resolvin D2 Limits Secondary Tissue Necrosis After Burn Wounds in Rats.

Project description:Secondary burn necrosis is the expansion and deepening of the original burn injury several days after injury. Limiting the extent of secondary burn necrosis may improve outcomes. In this study, we examined the ability of the lipid mediator of inflammation-resolution resolvin D2 (RvD2) and chromatin-lysing enzyme (DNase) to reduce secondary burn necrosis. Male Wistar rats were injured using a brass comb with 4 prongs heated in boiling water. This method created 2 parallel rows of 4 rectangular burned areas separated by 3 unburned interspaces. Starting at 2 hours after the burn injury, rats received either 25 ng/kg RvD2 intravenously daily for 7 days or 200 U/kg DNase every 12 hours for 3 days. We documented the necrosis around the initial wounds by digital photography. We used laser Doppler to assess the total blood flux in the burn area. We evaluated the functionality of the capillary network in the interspaces by optical coherence tomography angiography. We performed histological examination of wound skin tissue samples collected at 14 days postburn. We found that the interspace areas were preserved and had higher blood flow in the RvD2-treated group, while the burn areas expanded into the interspace areas, which were confluent by 7 days postburn, in the control-untreated group. We found a larger monocyte-to-neutrophil ratio in the RvD2-treated group compared with the DNase-treated and control groups (P < .05). Overall, RvD2 suppresses secondary necrosis and starts regeneration, highlighting the role of inflammation resolution as a potential therapeutic target in burn care.

| S-EPMC5832489 | biostudies-literature

Fibrillar collagen implicated in pregnancy-induced protection of mammary cancer

Project description:A suggested role for fibrillr collagen topology in the pregnancy-induced protection and invasive phenotype. Two conditions: RNA was isolated from murine mammary D2.OR cells cultured in fibrillar collagen I and non-fibrillar collagen I in 3D cell culture

2013-07-16 | E-GEOD-39539 | biostudies-arrayexpress

Resolvin D1 improves allograft osteointegration and directly enhances osteoblasts differentiation

Project description:Resolvin D1 improves allograft osteointegration and directly enhances osteoblasts differentiation

2023-02-08 | GSE224195 | GEO

Pseudoalteromonas tunicata D2 strain:D2

Project description:Pseudoalteromonas tunicata D2 strain:D2 Genome sequencing

| PRJNA196226 | ENA

Arthrobacter sp. D2 strain:D2

Project description:Arthrobacter sp. D2 strain:D2 Genome sequencing and assembly

| PRJNA314012 | ENA

Gene expression profile at single cell level of leukocytes from transplanted syngeneic left lung grafts following treatment with Resolvin D1.

Project description:Neutrophils play a pivotal role in the pathogenesis of lung ischemia-reperfusion injury. The effect of pro-resolving lipid mediators, such as Resolvin D1, on early neutrophil trafficking has not been assessed in organ transplantation. We obtained single-cell RNA sequencing of leukocytes from syngeneic left lung grafts to elucidate the genetic changes induced by recipient treatment with Resolvin D1 or vehicle.

2023-07-15 | GSE237110 | GEO

Kocuria rhizophila strain:D2 | isolate:D2

Project description:Kocuria rhizophila strain:D2 | isolate:D2 Genome sequencing and assembly

| PRJNA427247 | ENA

Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat.

Project description:The unprecedented increase in the prevalence of obesity and obesity-related disorders is causally linked to a chronic state of low-grade inflammation in adipose tissue. Timely resolution of inflammation and return of this tissue to homeostasis are key to reducing obesity-induced metabolic dysfunctions. In this study, with inflamed adipose, we investigated the biosynthesis, conversion, and actions of Resolvins D1 (RvD1, 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) and D2 (RvD2, 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid), potent anti-inflammatory and proresolving lipid mediators (LMs), and their ability to regulate monocyte interactions with adipocytes. Lipid mediator-metabololipidomics identified RvD1 and RvD2 from endogenous sources in human and mouse adipose tissues. We also identified proresolving receptors (i.e., ALX/FPR2, ChemR23, and GPR32) in these tissues. Compared with lean tissue, obese adipose showed a deficit of these endogenous anti-inflammatory signals. With inflamed obese adipose tissue, RvD1 and RvD2 each rescued impaired expression and secretion of adiponectin in a time- and concentration-dependent manner as well as decreasing proinflammatory adipokine production including leptin, TNF-α, IL-6, and IL-1β. RvD1 and RvD2 each reduced MCP-1 and leukotriene B₄-stimulated monocyte adhesion to adipocytes and their transadipose migration. Adipose tissue rapidly converted both resolvins (Rvs) to novel oxo-Rvs. RvD2 was enzymatically converted to 7-oxo-RvD2 as its major metabolic route that retained adipose-directed RvD2 actions. These results indicate, in adipose, D-series Rvs (RvD1 and RvD2) are potent proresolving mediators that counteract both local adipokine production and monocyte accumulation in obesity-induced adipose inflammation.

| S-EPMC3424332 | biostudies-literature

Gene expression profile of D2.OR-EGFP and D2.A1-EGFP cells in vitro and in vivo

Project description:We analysed gene expression profiles of D2.OR-EGFP and D2.A1-EGFP cells isolated from lungs and under standard in vitro conditions

2020-02-24 | GSE120628 | GEO

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