Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis

ABSTRACT: Patho-mechanistic origins and disease dynamics of ulcerative colitis are still poorly understood. The actin crosslinker Filamin A (FLNA) impacts cellular responses through interaction with numerous, cytosolic proteins. FLNA exists in two forms that differ only in a single amino acid: genome-encoded FLNAQ, and FLNAR - generated by post-transcriptional A-to-I editing. In the intestinal tract, FLNA is edited in fibroblasts, smooth muscle- and endothelial cells and we identified the FLNA editing status as a key determinant of colitis severity. FLNA editing was highest in healthy colons, and reduced during acute murine and human colitis. Mice that exclusively express edited FLNAR and do not downregulate editing upon challenge were highly resistant to DSS-induced colitis, whereas fully unedited FLNAQ animals developed severe inflammation. While the genetic induction of FLNA editing influenced the transcriptional states of intestinal structural cells and microbiome composition, we found that edited FLNAR exerts protection specifically via its influence on myeloid immune cells, which are not edited under physiological conditions. The introduction of a fixed FLNAR editing state, did not hamper normal cell migration but reduced macrophage inflammation and rendered neutrophils less prone to NETosis. We thus conclude that loss of FLNA editing correlates with colitis severity and targeted FLNA editing of myeloid cells might serve as novel therapeutic approach in intestinal inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE295910 | GEO | 2025/04/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis [RNA-Seq]

Project description:Patho-mechanistic origins and disease dynamics of ulcerative colitis are still poorly understood. The actin-crosslinker Filamin A (FLNA) impacts cellular responses through interaction with cytosolic proteins. FLNA exists in two forms that differ only in one amino acid: genome-encoded FLNAQ and FLNAR - generated by post-transcriptional A-to-I editing. FLNA is edited in fibroblasts, smooth muscle- and endothelial cells in the colon. We identified the FLNA editing status as a key determinant of colitis severity. FLNA editing was highest in healthy colons and reduced during acute murine and human colitis. Mice that exclusively express edited FLNAR and do not downregulate editing upon challenge were highly resistant to DSS-induced colitis, whereas fully unedited FLNAQ animals developed severe inflammation. While the genetic induction of FLNA editing influenced transcriptional states of structural cells and the microbiome composition, we found that FLNAR exerts protection specifically via its influence on myeloid cells, which are not edited under physiological conditions. Introducing fixed, fully edited FLNAR did not hamper normal cell migration but reduced macrophage inflammation and rendered neutrophils less prone to NETosis. In conclusion, loss of FLNA editing correlates with colitis severity, and targeted FLNA editing of myeloid cells might serve as a novel therapeutic approach in intestinal inflammation.

2025-05-03 | GSE296059 | GEO

Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis [scRNA-Seq]

2025-05-03 | GSE296058 | GEO

Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis

Project description:Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis

| PRJNA1256771 | ENA

Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis [RNA-Seq]

Project description:Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis [RNA-Seq]

| PRJNA1257421 | ENA

Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis [scRNA-Seq]

Project description:Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis [scRNA-Seq]

| PRJNA1257419 | ENA

The Refilin/Filamin complex regulates filipodia dynamics in oligodendrocyte progenitor cells.

Project description:Actin assembly and dynamics control the shape, motility and functions of diverse cell types. Programme for controlling theses dynamics is hard-coded into actin binding proteins and regulatory proteins. Refilins (RefilinA and RefilinB) are short lived regulatory proteins that interact with the actin-binding protein Filamin to convert it from an actin branching protein into one that bundles. We here show that different mechanisms converge to increase Refilin level in brain NG2+ precursor cells (polydendrocytes) committed to differentiate into the oligodendrocyte lineage. RefilinA is up-regulated through transcriptional activation during commitment into oligodendrocyte progenitor cells (OPC). RefilinB expression relies on PDGF signalling and is further stabilized by a unique auto-inhibitory domain masking the adjacent conserved PEST degradation signal. In NG2+ precursor cells and OPC, the RefilinB/Filamin complex localizes on filipodia protrusions and filipodial processes. Stable ectopic expression of Refilins in cells stimulates membrane remodelling dynamics linked with filipodia growth. These studies extend the function of the Refilin/FLNA complex to cell membrane remodelling linked with reorganization of underlying actin cytoskeleton. We performed whole transcriptomic analysis on the three cell population derived from OPC cells. Three different cultures were done and for each experiment we compared each cell population (NG2+, NG2+/A2B5 and O4) to the other 2 cell populations.

2013-05-01 | E-GEOD-37600 | biostudies-arrayexpress

Genome-Wide Analyses Identify Filamin-A (FLNA) as a Novel Downstream Target for Insulin and IGF1 Action.

Project description:Identification of filamin-A as a target for insulin and IGF1 action. Insulin analogues have been developed to achieve further improvement in the therapy of diabetes. However, modifications introduced into the insulin molecule might enhance their affinity to the insulin-like growth factor-1 receptor (IGF1R). Most tumors, including endometrial cancers, express high levels of IGF1R. The present study was aimed at identifying the entire set of genes that are differentially activated by insulin glargine or detemir, in comparison to regular insulin and IGF1, in Type 1 and Type 2 endometrial cancer cell lines (ECC-1 and USPC-1, respectively). Global gene expression analyses demonstrated a ligand-dependent up-regulated expression of filamin-A (FLNA), a gene that encodes an actin filament cross-linking protein, in both endometrial cancer cell types. Silencing experiments linked to migration assays confirmed the role of FLNA in cell growth and motility. Our data suggest that the activation of distinct sets of genes by glargine may lead to stimulation of specific pathways or, alternatively, may provide additive effects, different from those classically induced by insulin. Given that metastasis is one of the major factors contributing to the aggressiveness of tumors, the identification of FLNA as a downstream target for insulin-like hormones may be of translational relevance in cancer research. Clinical studies in endometrial cancer may add further relevant information regarding the possible differential actions of insulin analogues with respect to native insulin.

2019-01-02 | GSE109022 | GEO

The Refilin/Filamin complex regulates filipodia dynamics in oligodendrocyte progenitor cells.

2013-05-01 | GSE37600 | GEO

DSS Microbiota LC-MS/MS

Project description:In the DSS-induced colitis model, the epithelial damage and resulting inflammation is restricted to the colon, with a potential influence on the microbial composition in the adjacent cecum. Several studies have reported changes of the gut microbiota in the DSS-induced colitis model and other mouse models of IBD. Furthermore, metaproteomics analysis of the gut microbiome in a mouse model of Crohn’s disease demonstrated that disease severity and location are microbiota-dependent, with clear evidence for the causal role of bacterial dysbiosis in the development of chronic ileal inflammation. We have developed a refined model of chronic DSS-induced colitis that reflects typical symptoms of human IBD without a risky body weight loss usually observed in DSS models [Hoffmann et al., submitted]. In this study, we used metaproteomics to characterize the disease-related changes in bacterial protein abundance and function in the refined model of DSS-induced colitis. To assess the structural and functional changes, we applied 16S rRNA gene sequencing and metaproteomics analysis of the intestinal microbiota in three different entities of the intestinal environment, i.e. colon mucus, colon content and cecum content.

2020-03-17 | PXD007220 | Pride

Genome-Wide Analyses Identify Filamin-A (FLNA) as a Novel Downstream Target for Insulin and IGF1 Action.

Project description:Genome-Wide Analyses Identify Filamin-A (FLNA) as a Novel Downstream Target for Insulin and IGF1 Action.

| PRJNA429450 | ENA