Transcriptomics

Dataset Information

0

Perilipin 2-positive mononuclear phagocytes accumulate in diabetic retina and promote PPARγ-dependent vasodegeneration


ABSTRACT: Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia leads to non-proliferative diabetic retinopathy (NPDR). NPDR is associated with blood-retinal barrier disruption, plasma exudates, microvascular degeneration, elevated inflammatory cytokine levels and monocyte (Mo) infiltration. Whether and how the diabetes-associated changes in plasma lipid and carbohydrate levels modify Mo differentiation. Here, we show that mononuclear phagocytes (MPs) in areas of vascular leakage in DR donor retinas express PLIN2, a marker of intracellular lipid load. Strong upregulation of PLIN2 was also observed when healthy donor Mos were treated with plasma from T2DM patients or with palmitate concentrations typical of T2DM plasma, but not under high glucose conditions. PLIN2 expression correlated with the expression of other key genes involved in lipid metabolism (ACADVL, PDK4) and the DR biomarkers ANGPTL4 and CXCL8. Mechanistically, we show that lipid-exposed MPs induce capillary degeneration in ex vivo explants, which was inhibited by pharmaceutical inhibition of PPARγ signaling. Our study provides a novel mechanism linking dyslipidemia-induced MP polarization to the increased inflammatory cytokine levels and microvascular degeneration that characterize NPDR. This study provides comprehensive insights into the glycemia-independent activation of Mos in T2DM and identifies MP PPARγ as a target to inhibit lipid-activated MPs in DR

ORGANISM(S): Homo sapiens

PROVIDER: GSE239512 | GEO | 2023/08/31

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2022-09-06 | GSE212594 | GEO
2012-06-08 | E-GEOD-38590 | biostudies-arrayexpress
2023-10-13 | GSE214064 | GEO
2022-04-06 | GSE193613 | GEO
2019-06-19 | GSE132911 | GEO
2012-07-12 | GSE37575 | GEO
2012-06-09 | GSE38590 | GEO
2016-12-31 | GSE77208 | GEO
2019-12-05 | GSE110013 | GEO
2022-02-28 | PXD002026 | Pride