Related Experiment Video
Updated: Dec 22, 2025
10:31
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
527
Signaling pathways predisposing to chronic kidney disease progression
Mohamad Zaidan1,2, Martine Burtin1, Jitao David Zhang3
1Institut National de la Santé et de la Recherche Médicale (INSERM), U1151, CNRS UMR 8253, Institut Necker Enfants Malades (INEM), Department of Growth and Signaling, Université de Paris, Paris, France.
JCI Insight
|May 8, 2020
Summary
Kidney injury triggers compensatory growth, but in some mice, this activates a type I interferon response, leading to cell cycle arrest and chronic kidney disease. This interferon response is a key driver of renal lesion development.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Kidney injury causes compensatory nephron growth, which can paradoxically lead to chronic kidney disease.
- The molecular pathways driving these pathological alterations after nephron loss are not well understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying pathological changes following nephron reduction.
- To identify signaling pathways involved in the development of renal lesions after compensatory growth.
Main Methods:
- Utilized genetically distinct mouse strains with differential responses to nephron reduction.
- Performed temporal genome-wide transcriptome studies and molecular analyses.
- Employed coinertia analysis for gene expression clustering.
Main Results:
- Identified two distinct waves of cell proliferation and gene expression post-nephron reduction.
- Discovered a type I interferon (IFN) response as an early, specific signature in sensitive mice, correlating with cell cycle arrest.
- Demonstrated that inducing type I IFN response in resistant mice caused renal lesions.
Conclusions:
- Early molecular and cellular events after nephron reduction dictate the risk of developing late renal lesions.
- Type I IFN response is a critical factor in the progression of kidney damage and chronic kidney disease development.
Related Concept Videos
01:25Chronic Kidney Disease I: Introduction
472
Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage renal disease. At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate for...
472
01:28Chronic Kidney Disease III: Interprofessional Care
268
Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
268
01:24Chronic Kidney Disease II: Clinical Manifestations
460
Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...
460
01:29Acute Kidney Injury II: Pathophysiology
727
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...
727
01:10Nephrons
5.9K
The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma...
5.9K
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
208
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...
208