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Related Concept Videos

Acute Kidney Injury II: Pathophysiology01:29

Acute Kidney Injury II: Pathophysiology

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Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
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Acute Kidney Injury I: Introduction01:22

Acute Kidney Injury I: Introduction

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Introduction:Acute Kidney Injury (AKI) describes a swift decrease in kidney function occurring over hours to days, characterized by the kidneys' failure to remove waste products from the bloodstream. This leads to dangerous complications like metabolic acidosis, fluid overload, and electrolyte imbalances, such as hyperkalemia, which can cause life-threatening arrhythmias. AKI is common in both hospital and outpatient settings, often triggered by dehydration, sepsis, or exposure to nephrotoxic...
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Acute Kidney Injury III: Clinical Manifestations01:29

Acute Kidney Injury III: Clinical Manifestations

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Acute Kidney Injury (AKI) progresses through distinct clinical phases: the oliguric, diuretic, and recovery phases, each marked by unique manifestations and challenges.Oliguric Phase:The oliguric phase is the initial stage of AKI, typically lasting 10 to 14 days. This phase is marked by a significant reduction in urine output, usually less than 400 mL per day, indicating decreased kidney function. Fluid retention is a prominent feature, leading to symptoms such as edema, hypertension, and...
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Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

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Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
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The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Histone Modification02:32

Histone Modification

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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
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Related Experiment Video

Updated: Jan 14, 2026

Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
06:23

Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells

Published on: November 21, 2025

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Histone Lactylation-Mediated PAD4 Up-Regulation Promotes Septic Acute Kidney Injury via Activating NETosis.

Wen-Lin Huang1, Yan-Chen Wang2, Tian-le Cheng1

  • 1Department of Urology, Zhuzhou Hospital, Xiangya Medical College, Central South University, Zhuzhou, China.

Nephrology (Carlton, Vic.)
|October 17, 2025
PubMed
Summary
This summary is machine-generated.

Septic acute kidney injury (SAKI) involves neutrophil extracellular trap formation (NETosis). This study reveals p300-mediated H3K18 lactylation enhances peptidyl arginine deiminase 4 (PAD4) expression, promoting NETosis and SAKI. Targeting PAD4 may treat SAKI.

Keywords:
NETosisPAD4histone lactylationseptic acute kidney injury

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Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Neutrophil extracellular trap formation (NETosis) plays a role in septic acute kidney injury (SAKI) pathogenesis.
  • The precise molecular mechanisms regulating NETosis in SAKI are not fully understood.

Purpose of the Study:

  • To investigate the role of peptidyl arginine deiminase 4 (PAD4) in NETosis during SAKI.
  • To elucidate the potential molecular mechanism involving PAD4 in SAKI.

Main Methods:

  • Established a rat model of SAKI using cecal ligation and puncture (CLP) and stimulated NRK-52E cells with lipopolysaccharides (LPS) in vitro.
  • Assessed kidney injury via HE staining, serum urea nitrogen, creatinine, and lactate levels.
  • Quantified target molecule expression using qRT-PCR, Western blotting, and immunofluorescence for citrullinated histone H3 (citH3).
  • Analyzed p300 binding to the PAD4 promoter using chromatin immunoprecipitation (ChIP).

Main Results:

  • PAD4 and serum lactate levels were significantly elevated in SAKI rats and positively correlated.
  • H3K18 lactylation levels doubled in the kidneys of CLP rats.
  • p300-mediated H3K18 lactylation was found to enhance PAD4 expression in response to LPS stimulation.
  • Inhibition of PAD4 or histone lactylation suppressed NETosis and alleviated SAKI in rats.

Conclusions:

  • p300-mediated H3K18 lactylation enhances PAD4 expression, thereby promoting NETosis and contributing to SAKI.
  • These findings suggest PAD4 as a potential therapeutic target for SAKI.