MicroRNA-252 and FoxO repress inflammaging by a dual inhibitory mechanism on Dawdle mediated TGF-β pathway in Drosophila muscle
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA597884 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The abstract for the manuscript Inflammaging refers to low-grade, chronically activated innate immunity that negatively impacts adult survival. However, little is known about the intrinsic signaling pathway that upregulates innate immune genes during aging. Here using Drosophila melanogaster, we profile the microRNA targetomes in young and aged animals, and reveal Dawdle (Daw), an activin-like ligand of the TGF-beta pathway, as a physiological target of microRNA-252 (miR-252). We show that miR-252 cooperates with the transcriptional regulation of Daw by Forkhead box O (FoxO), a conserved transcriptional factor implicated in aging, at the post-transcriptional levels. Unopposed Daw triggers hyper activation of innate immune genes coupled with a catastrophic decline in organismal survival. Single-cell sequencing analysis describes a non-cell autonomous regulation between Daw and the induction of innate immune genes in the muscle. We further determine the downstream cascade by which Daw signaling leads to increased Kenny /IKKgamma protein, which in turn activates Relish/NF-kappaB protein and consequentially upregulation of innate immune genes. Finally, while aging leads to a decline in FoxO activity, transgenic increase of miR-252 and FoxO pathway factors in wild-type Drosophila extends lifespan and mitigates the induction of innate immune genes in aging. Together, we propose that miR-252 and FoxO repress inflammaging by cooperative inhibition of Daw mediated TGF-beta pathway.
2021-01-01 | GSE142655 | GEO
Project description:Innate immunity is a highly reactive response aiming at clearing pathogens. Abnormal induction of innate immune genes can lead to deleterious consequences to the host. However, little is known about the intrinsic signaling pathway that prohibits constitutive activation of innate immunity. Here using fruit flies, we profile the microRNA targetomes in young and aged animals. We demonstrate FoxO, and miR-252 inhibit spontaneous induction of innate immunity by repressing Daw. We further determine the signaling cascade by which Daw causes the reduction of Atg8a-mediated selective autophagy on kenny protein, which in turn activates Relish protein and consequential upregulation of innate immune genes. Finally, while aging leads to a decline in FOXO signaling activity concomitant with a progressive induction of innate immune genes, transgenic increase of FoxO, miR-252, and Atg8a in wild-type Drosophila promotes longevity and mitigates the expression of age-onset innate immune genes. Together, we propose that FoxO and miR-252 define a pro-survival mechanism by inhibiting constitutive innate immunity.
2018-12-31 | GSE124504 | GEO
Project description:microRNA-252 and FoxO regulate inflammaging through dual inhibition on Dawdle/Acticin of TGF-β pathway in Drosophila
| PRJNA512241 | ENA
Project description:Aerococcaceae bacterium zg-252 isolate:zg-252 Genome sequencing
| PRJNA685286 | ENA
Project description:Aging is accompanied by chronic, low-grade systemic inflammation, termed inflammaging, a main driver of age-associated diseases. Such sterile inflammation is typically characterized by elevated levels of pro-inflammatory mediators, such as cytokines and reactive oxygen species causing organ damage. Lipid mediators play important roles in the fine-tuning of both the promotion and the resolution of inflammation. Yet, it remains unclear how lipid mediators fit within the concept of inflammaging and how their biosynthesis and function is affected by aging. Here, we provide comprehensive signature profiles of inflammatory markers in organs afflicted with inflammation of young and old C57BL/6 mice. We reveal an organ-specific footprint of inflammation-related cytokines, chemokines and lipid mediators, which are distinctively affected by aging. While some organs are characterized by a pronounced pro-inflammatory microenvironment and impaired resolution during aging, others display elevated levels of pro-resolving mediators or an overall decrease in inflammatory signaling. Our results demonstrate that it proves difficult to establish a unifying concept for alterations of immunomodulatory mediators as consequence of aging and that organ specificity needs to be considered. Moreover, our data imply that inclusion of lipid mediators into the concept of inflammaging provides a comprehensive tool to characterize the inflammatory microenvironment during aging on a broader and yet, more detailed scope.
2021-03-22 | PXD024356 | Pride
Project description:We performed RNA-seq for WT and foxo mutant flies, by combining with Dr. Baihua's foxo chip-seq data, we found 101 foxo-repressed and 300 foxo-activated genes. By analyzing expression change of these genes during age, we found foxo-repressed genes became activated, while foxo-activated genes became repressed, suggesting foxo signaling declines with age.
2018-11-14 | GSE122470 | GEO
Project description:Facklamia sp. 252 Genome sequencing and assembly
| PRJNA591105 | ENA
Project description:Neurospora crassa strain:252 Genome sequencing
| PRJNA250326 | ENA
Project description:Low-grade chronic inflammation is considered a hallmark of ageing and associated with impaired tissue function and development of disease. However, how cell-intrinsic and -extrinsic factors interact to establish this phenotype, termed inflammaging, remains poorly understood. We addressed this question in the mouse intestinal epithelium, using organoid cultures to dissect stem cell-intrinsic and -extrinsic sources of increased inflammatory signaling upon ageing. At the single-cell level, we found that inflammaging establishes differently in cells along the crypt-villus axis, including intestinal stem cells (ISCs). Importantly, the inflammaging phenotype was stably propagated by aged ISCs in organoid cultures and associated with increased chromatin accessibility of inflammation-associated loci in vivo and ex vivo, indicating a cell-intrinsic memory of inflammation. Mechanistically, we show that expression of inflammaging genes is dependent on STAT1 signaling. Together, our data reveal that inflammaging in the intestine is promoted by a cell-intrinsic mechanism, stably propagated by ISCs and associated with a disbalance in immune homeostasis.
2023-10-26 | GSE233898 | GEO
Project description: Not available
| S-EPMC7399912 | biostudies-literature