Identification of fibroblast activation-related genes in two acute kidney injury models

Weiming Deng1, Xiangling Wei1, Zhanwen Dong1

  • 1Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.

Peerj
|March 29, 2021
PubMed
Abstract

Insights

This study identifies key genes like Hnf4α, Pck1, and Timp-1 involved in fibroblast activation during acute kidney injury (AKI). These findings offer potential therapeutic targets for preventing renal fibrosis progression.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Genomics

Background:

  • Acute kidney injury (AKI) from ischemia-reperfusion or nephrotoxicity can progress to chronic kidney disease (CKD).
  • Early fibroblast activation is a critical but understudied factor in AKI to CKD transition.
  • This study investigates gene expression changes related to fibroblast activation in AKI models.

Purpose of the Study:

  • To identify genes and pathways associated with fibroblast activation in AKI.
  • To explore the role of fibroblast activation in the progression from AKI to CKD.
  • To find potential biomarkers for early AKI detection and therapeutic targets.

Main Methods:

  • Analysis of microarray expression profiles (GSE62732, GSE121190) to identify differentially expressed genes (DEGs).
  • Utilized R software, Gene Ontology (GO), DAVID, KEGG, STRING, and Cytoscape for data analysis and network construction.
  • Validated hub gene expression in a Hypoxia/Reoxygenation (H/R) cell model using qRT-PCR.

Main Results:

  • Identified 457 DEGs, with 215 upregulated and 242 downregulated in injured kidney samples.
  • GO analysis revealed DEGs involved in transport, oxidation-reduction, and metabolic processes.
  • KEGG pathway analysis highlighted enrichment in PI3K-Akt signaling, protein digestion/absorption, and focal adhesion pathways.
  • Validated Hnf4α, Pck1, and Timp1 as hub genes in the H/R model.

Conclusions:

  • Hnf4α, Pck1, and Timp-1 are identified as key players in early fibroblast activation.
  • These genes may serve as novel therapeutic targets for early prediction and treatment of renal fibrosis.
  • Understanding fibroblast activation pathways is crucial for managing AKI progression to CKD.

Related Concept Videos

Acute Kidney Injury II: Pathophysiology01:29

Acute Kidney Injury II: Pathophysiology

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...
508
Acute Kidney Injury I: Introduction01:22

Acute Kidney Injury I: Introduction

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...
252
Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

Acute Kidney Injury IV: Diagnostic Studies and Prevention

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...
127
Introduction to Fibroblasts01:09

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.3K
Acute Kidney Injury III: Clinical Manifestations01:29

Acute Kidney Injury III: Clinical Manifestations

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...
401