Related Experiment Video
Updated: Feb 13, 2026
08:53
Analysis of Nephron Composition and Function in the Adult Zebrafish Kidney
Published on: August 9, 2014
45.5K
Single-nephron proteomes connect morphology and function in proteinuric kidney disease
Martin Höhne1, Christian K Frese2, Florian Grahammer3
1Department II of Internal Medicine, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Cologne, Germany.
Kidney International
|March 14, 2018
Summary
Researchers developed a novel mass spectrometry method to analyze kidney disease at the single-nephron level. This approach revealed altered protein homeostasis and identified lysosomal proteins as potential therapeutic targets in proteinuric kidney diseases.
Area of Science:
- Nephrology
- Proteomics
- Molecular Biology
Background:
- Heterogeneous organ damage impacts disease prognosis, but molecular analysis of individual functional units is challenging.
- Proteinuric glomerular kidney diseases affect glomeruli and tubules variably, lacking specific treatments.
- Understanding molecular heterogeneity is crucial for deciphering pathological mechanisms.
Purpose of the Study:
- To develop and apply a mass spectrometry-based method for analyzing proteome heterogeneity in individual nephron segments.
- To investigate molecular mechanisms underlying proteinuric kidney diseases at a sub-biopsy scale.
- To identify potential therapeutic targets by examining protein expression modules.
Main Methods:
- Developed a mass spectrometry-based methodology for proteomic analysis of individually isolated nephron segments.
- Applied the method to single glomeruli from mouse models of sclerotic glomerular disease.
- Analyzed glomeruli from patients with genetic sclerotic and non-sclerotic proteinuric diseases.
Main Results:
- Identified a protein expression module in mouse glomeruli including extracellular matrix proteins, albumin, and LAMP1, associated with glomerular sclerosis and podocyte marker loss.
- Demonstrated that genetic ablation of LAMP1-correlated lysosomal proteases ameliorated glomerular damage in vivo.
- Observed increased lysosomal proteins and decreased mutated gene products in human proteinuric kidney disease glomeruli.
Conclusions:
- Altered protein homeostasis (proteostasis) is a conserved mechanism in proteinuric kidney diseases.
- Lysosomal proteins represent potential therapeutic targets for proteinuric kidney diseases.
- The developed technology enables capturing intra-individual variability in kidney and other tissue diseases.
Related Concept Videos
01:10Nephrons
7.2K
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...
7.2K
01:45Kidney Structure
75.5K
The kidneys are two large bean-shaped organs located in the upper abdomen. They filter the blood several times a day to remove toxins and rebalance water and electrolytes of the circulatory system via the renal veins. The kidneys receive blood directly from the heart via the renal arteries. These arteries enter the kidney at the hilum, the concave surface of the bean, where they branch and divide into smaller vessels and capillaries.
75.5K
01:17Functions of Connective Tissues
17.2K
Connective tissues perform a broad range of functions in the body. Their primary function is to connect and link different tissues in the body and act as packaging material between tissues. The areolar tissue, a connective tissue prototype, commonly cements various tissue types in diverse body organs. In contrast, adipose tissue cushions internal organs while insulating the body from heat loss.
Hard connective tissues, such as bones and cartilage, provide structure and support to the body.
Hard connective tissues, such as bones and cartilage, provide structure and support to the body.
17.2K
01:25Chronic Kidney Disease I: Introduction
768
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...
768
01:24Chronic Kidney Disease II: Clinical Manifestations
688
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...
688
01:28Chronic Kidney Disease III: Interprofessional Care
485
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...
485