Dataset Information

Psychological Stress-Induced Systemic Corticosterone Directly Sabotages Intestinal Stem Cells Activity

ABSTRACT: Stress exerts profound impacts on the gastrointestinal tract, yet its effects on intestinal stem cells (ISCs) have not been fully explored. Here, we unveiled a notable reduction in both the quantity and proliferative capacity of ISCs under chronic stress condition, which was mediated by elevated corticosterone levels resulting from the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Mechanistically, corticosterone directly impairs ISCs by interacting with its receptor, nuclear receptor subfamily 3 group c member 1 (NR3C1), which promoted FKBP prolyl isomerase 5 (FKBP5) expression to negatively regulate the AKT activation by mediating the dephosphorylation at the Ser473, thus enhancing the nuclear translocation of the forkhead box O (FoxO) to inhibit the proliferative activity. Collectively, these findings provide a novel mechanistic insight into the deleterious effects of psychological stress on gut, and underscore corticosterone as a key mediator linking stress to ISCs dysfunction.

ORGANISM(S): Mus musculus

PROVIDER: GSE253827 | GEO | 2025/03/14

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: The epididymis has long been of interest owing to its role in promoting the functional maturation of the male germline. More recent evidence has also implicated the epididymis as an important sensory tissue responsible for remodeling of the sperm epigenome, both under physiological conditions and in response to diverse forms of environmental stress. Despite this knowledge, the intricacies of the molecular pathways involved in regulating the adaptation of epididymal tissue to paternal stressors remains to be fully resolved. Objective: The overall objective of this study was to investigate the direct impact of corticosterone challenge on a tractable epididymal epithelial cell line (i.e., mECap18 cells) in terms of driving adaptation of the cellular proteome and phosphoproteome signaling networks. Materials and methods: The newly developed phosphoproteomic platform EasyPhos coupled with sequencing via an Orbitrap Exploris 480 mass spectrometer was applied to survey global changes in the mECap18 cell (phospho)proteome resulting from sub-chronic (10-day) corticosterone challenge.Results: The imposed corticosterone exposure regimen elicited relatively subtle modifications of the global mECap18 proteome [i.e., only 73/4171 (~1.8%) proteins displayed altered abundance]. By contrast, ~15% of the mECap18 phosphoproteome was substantially altered following corticosterone challenge. In-silico analysis of the corresponding parent proteins revealed an activation of pathways linked to DNA damage repair and oxidative stress responses as well as a reciprocal inhibition of pathways associated with organismal death. Corticosterone challenge also induced the phosphorylation of several proteins linked to the biogenesis of microRNAs. Accordingly, orthogonal validation strategies confirmed an increased in DNA damage, which was ameliorated upon selective kinase inhibition, and an altered abundance profile of a subset of microRNAs in corticosterone-treated cells. Conclusions: Together, these data confirm that epididymal epithelial cells are reactive to corticosterone challenge and that their response is tightly coupled to the opposing action of cellular kinases and phosphatases.

Dataset Information

Psychological Stress-Induced Systemic Corticosterone Directly Sabotages Intestinal Stem Cells Activity

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets