Apoptosis, fibrosis and senescence
1Division of Nephrology, Department of Internal Medicine, University of Virginia, Charlottesville, Va., USA.
Nephron. Clinical Practice
|October 25, 2014
Summary
Kidney fibrosis involves inflammation and cell death. Targeting tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and preserving proximal tubule cell integrity may offer new therapeutic strategies for kidney disease.
Area of Science:
- Nephrology
- Cellular Biology
- Molecular Medicine
Background:
- Kidney fibrosis is a key feature of progressive kidney disease.
- Mechanisms include inflammation, oxidative stress, and proximal tubule cell death (apoptosis/senescence).
Purpose of the Study:
- To review current evidence on kidney fibrosis development.
- To discuss potential molecular mechanisms and therapeutic targets.
Main Methods:
- Review of recent studies on renal fibrosis.
- Analysis of cellular mechanisms and cytokine involvement.
- Examination of lineage tracing and gene expression data.
Main Results:
- TWEAK (tumor necrosis factor-like weak inducer of apoptosis) mediates kidney inflammation and fibrosis.
- Inhibiting apoptosis via TWEAK blockade reduces kidney fibrosis.
- Pericytes/perivascular fibroblasts differentiate into myofibroblasts.
- Peroxisome proliferator-activated receptor-α activation reduces fibrosis markers.
Conclusions:
- TWEAK inhibition is a potential therapeutic strategy for kidney fibrosis.
- Preserving proximal tubule cell metabolism and integrity is a promising therapeutic target.
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