Asset Details
Do you wish to reserve the book?
Multi-Omics Integration Identifies TNFRSF1A as a Causal Mediator of Immune Microenvironment Reprogramming in Diabetic Kidney Disease
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Multi-Omics Integration Identifies TNFRSF1A as a Causal Mediator of Immune Microenvironment Reprogramming in Diabetic Kidney Disease
Do you wish to request the book?
Multi-Omics Integration Identifies TNFRSF1A as a Causal Mediator of Immune Microenvironment Reprogramming in Diabetic Kidney Disease
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Multi-Omics Integration Identifies TNFRSF1A as a Causal Mediator of Immune Microenvironment Reprogramming in Diabetic Kidney Disease
2025
Overview
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease worldwide. However, the inflammatory mediators that causally drive disease progression remain incompletely defined. In this study, we used a multi-omics approach that combined single-cell RNA sequencing, spatial transcriptomics, pseudotime trajectory analysis, cell-to-cell communication analysis, and Mendelian randomization (MR) to investigate the role of tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in DKD development. Findings were further validated in zebrafish embryos depleted of pdx1, an established model of DKD. Spatial transcriptomic analysis showed that TNFRSF1A is enriched in cortical kidney regions. Pseudotime analysis revealed progressive immune reprogramming, with an early predominance of T and NK cells and gradual shift to myeloid infiltration and B-cell expansion. Cell-to-cell communication analysis highlighted IL-1β and related signaling pathways that increase NF-κB activity. Mendelian Randomization analysis, complemented by PPI network mapping, identified TNFRSF1A (OR = 1.78, 95% CI: 1.17–2.71, p = 0.007) as a gene with genetic evidence supporting a causal association. Consistent with the human data, experiments in zebrafish showed that TNFRSF1A expression increases significantly following pdx1 knockdown (p = 0.0025). Together, these findings support a role for TNFRSF1A in immune microenvironment reprogramming in DKD, while not excluding the involvement of additional regulatory pathways.
Publisher
MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
Subject
/ B cells
/ Cellular Microenvironment - immunology
/ Diabetes
/ Diabetic Nephropathies - genetics
/ Diabetic Nephropathies - immunology
/ Diabetic Nephropathies - metabolism
/ Diabetic Nephropathies - pathology
/ Genes
/ Genetics
/ Humans
/ Ligands
/ Receptors, Tumor Necrosis Factor, Type I - genetics
/ Receptors, Tumor Necrosis Factor, Type I - metabolism
/ RNA
