Inflammation primes the kidney for recovery by activating AZIN1 A-to-I editing DOI Creative Commons
Segewkal Heruye, Jered Myslinski, Chao Zeng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 9, 2023

Abstract The progression of kidney disease varies among individuals, but a general methodology to quantify timelines is lacking. Particularly challenging the task determining potential for recovery from acute injury following various insults. Here, we report that quantitation post-transcriptional adenosine-to-inosine (A-to-I) RNA editing offers distinct genome-wide signature, enabling delineation trajectories in kidney. A well-defined murine model endotoxemia permitted identification origin and extent A-to-I editing, along with temporally discrete signatures double-stranded stress Adenosine Deaminase isoform switching. We found Antizyme Inhibitor 1 (AZIN1), positive regulator polyamine biosynthesis, serves as particularly useful temporal landmark during endotoxemia. Our data indicate AZIN1 triggered by preceding inflammation, primes activates endogenous mechanisms. By comparing genetically modified human cell lines mice locked either edited or uneditable states, uncovered not only enhances biosynthesis also engages glycolysis nicotinamide drive phenotype. findings implicate quantifying could potentially identify individuals who have transitioned an phase. This phase would reflect their past inflammation future recovery.

Language: Английский

The key role of altered tubule cell lipid metabolism in kidney disease development DOI Creative Commons
Lauren E. Lee, Tomohito Doke, Dhanunjay Mukhi

et al.

Kidney International, Journal Year: 2024, Volume and Issue: 106(1), P. 24 - 34

Published: April 16, 2024

Kidney epithelial cells have very high energy requirements, which are largely met by fatty acid oxidation. Complex changes in lipid metabolism observed patients with kidney disease. Defects oxidation and increased uptake, especially the context of hyperlipidemia proteinuria, contribute to this excess build-up exacerbate disease development. Recent studies also highlighted role de novo lipogenesis fibrosis. The defect causes starvation. Increased synthesis, lower can cause toxic build-up, reactive oxygen species generation, mitochondrial damage. A better understanding these metabolic processes may open new treatment avenues for diseases targeting metabolism.

Language: Английский

Citations

22
G-protein coupled receptor GPR124 protects against podocyte senescence and injury in diabetic kidney disease. DOI
Yujia Li,

Yiqi Duan,

Qingqing Chu

et al.

Kidney International, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Kidney immunology from pathophysiology to clinical translation DOI
Christian Kurts, Sibylle von Vietinghoff, Christian F. Krebs

et al.

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Language: Английский

Citations

1
Comprehensive profiling of cell type-specific expression and distribution of complement genes in mouse and human kidneys: insights into normal physiology and response to kidney transplantations DOI Creative Commons
Xianzhi Li,

Li Zhu

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: Feb. 27, 2025

Background Recent studies innovatively revealed the localized expression of complement genes in kidneys and shed light on vital roles intracellular system physiologic function pathological conditions. However, a comprehensive analysis context evolving cellular landscape kidney is not available.

Language: Английский

Citations

0
Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury DOI Creative Commons
Megan L. Baker, Lloyd G. Cantley

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: 135(6)

Published: March 16, 2025

Acute kidney injury (AKI) encompasses pathophysiology ranging from glomerular hypofiltration to tubular cell and outflow obstruction. This Review will focus on the tubulointerstitial processes that underlie most cases of AKI. Tubular epithelial (TEC) can occur via distinct insults, including ischemia, nephrotoxins, sepsis, primary immune-mediated processes. Following these initial cells activate survival repair responses or they develop mitochondrial dysfunction metabolic reprogramming, cell-cycle arrest, programmed death. Developing evidence suggests fate individual survive proliferate undergo death senescence is frequently determined by a biphasic immune response with proinflammatory macrophage, neutrophil, lymphocyte infiltration exacerbating activating death, while alternatively activated macrophages specific subsets subsequently modulate inflammation promote repair. Functional recovery requires this reparative phase supports proteolytic degradation casts, proliferation surviving TECs, restoration TEC differentiation. Incomplete resolution persistence lead failed repair, fibrosis, chronic disease. Despite extensive research in animal models, translating preclinical findings therapies remains challenging, emphasizing need for integrated multiomic approaches advance AKI understanding treatment.

Language: Английский

Citations

0
Application and Progression of Single‐Cell RNA Sequencing in Diabetes Mellitus and Diabetes Complications DOI Creative Commons

Jiajing Hong,

Shiqi Lu,

Guohui Shan

et al.

Journal of Diabetes Research, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Diabetes is a systemic metabolic disorder primarily caused by insulin deficiency and resistance, leading to chronic hyperglycemia. Prolonged diabetes can result in damage multiple organs, including the heart, brain, liver, muscles, adipose tissue, thereby causing various fatal complications such as diabetic retinopathy, cardiomyopathy, nephropathy. Single‐cell RNA sequencing (scRNA‐seq) has emerged valuable tool for investigating cell diversity pathogenesis of identifying potential therapeutic targets or complications. This review provides comprehensive overview recent applications scRNA‐seq diabetes‐related researches highlights novel biomarkers immunotherapy with cell‐type information its associated

Language: Английский

Citations

0
The actin and microtubule network regulator WHAMM is identified as a key kidney disease risk gene DOI
Dhanunjay Mukhi,

Lakshmi P. Kolligundla,

Tomohito Doke

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115462 - 115462

Published: March 27, 2025

Language: Английский

Citations

0
The critical role of endoplasmic reticulum stress and the stimulator of interferon genes (STING) pathway in kidney fibrosis. DOI
Magaiver Andrade-Silva,

Poonam Dhillon,

Andrea Sánchez‐Navarro

et al.

Kidney International, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

3
Comparative Analysis of Acute Kidney Injury Models and Related Fibrogenic Responses: Convergence on Methylation Patterns Regulated by Cold Shock Protein DOI Creative Commons
Sabine Brandt,

Anja Bernhardt,

Saskia Häberer

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 367 - 367

Published: Feb. 20, 2024

Background: Fibrosis is characterized by excessive extracellular matrix formation in solid organs, disrupting tissue architecture and function. The Y-box binding protein-1 (YB-1) regulates fibrosis-related genes (e.g., Col1a1, Mmp2, Tgfβ1) contributes significantly to disease progression. This study aims identify fibrogenic signatures the underlying signaling pathways modulated YB-1. Methods: Transcriptomic changes associated with gene patterns human chronic kidney diseases murine acute injury models were analyzed a focus on known YB-1 targets. Ybx1-knockout mouse strains (Ybx1ΔRosaERT+TX Ybx1ΔLysM) subjected various models. histopathological staining, transcriptome analysis, qRT-PCR, methylation zymography, Western blotting. Results: Integrative transcriptomic analyses revealed that involved several related matrisome, WNT, YAP/TAZ, TGFß pathways, Klotho expression. Changes status of promoter specific methyltransferases (DNMT) are linked expression, extending other genes. Notably, kidney-resident cells play significant role YB-1-modulated signaling, whereas infiltrating myeloid immune have minimal impact. Conclusions: emerges as master regulator fibrogenesis, guiding DNMT1 highlights potential target for epigenetic therapies interfering this process.

Language: Английский

Citations

2
Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing DOI Creative Commons
Segewkal Heruye, Jered Myslinski, Chao Zeng

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(17)

Published: July 2, 2024

The progression of kidney disease varies among individuals, but a general methodology to quantify timelines is lacking. Particularly challenging the task determining potential for recovery from acute injury following various insults. Here, we report that quantitation post-transcriptional adenosine-to-inosine (A-to-I) RNA editing offers distinct genome-wide signature, enabling delineation trajectories in kidney. A well-defined murine model endotoxemia permitted identification origin and extent A-to-I editing, along with temporally discrete signatures double-stranded stress adenosine deaminase isoform switching. We found antizyme inhibitor 1 (AZIN1), positive regulator polyamine biosynthesis, serves as particularly useful temporal landmark during endotoxemia. Our data indicate AZIN1 triggered by preceding inflammation, primes activates endogenous mechanisms. By comparing genetically modified human cell lines mice locked either A-to-I-edited or uneditable states, uncovered not only enhances biosynthesis also engages glycolysis nicotinamide drive phenotype. findings implicate quantifying could potentially identify individuals who have transitioned an phase. This phase would reflect their past inflammation future recovery.

Language: Английский

Citations

2