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Identification of genes specifically expressed in chronic and progressive glomerulosclerosis
1Department of Medicine II, Niigata University Medical School, Japan. naritai@med.niigata-u.ac.jp
Abstract:
To identify genes expressed predominantly in the kidney with chronic and progressive glomerulosclerosis but not in acute and transient form of glomerulonephritis, we induced progressive glomerulosclerosis in rats by applying unilateral nephrectomy prior to injection of monoclonal anti-Thy1.1 antibody (OX-7), which cause acute and transient glomerulonephritis with single injection. In rats with nephrectomy and OX-7 injection (Nx group), proteinuria increased with time and mesangial expansion accompanied with interstitial fibrosis was recognized, whereas transient proteinuria and mesangiolysis followed by mesangial hypercellularity were seen in rats with sham operation and OX-7 injection (Sham group). Four weeks after the induction of glomerulonephritis, mRNAs were isolated from kidney cortex of both groups and used for cDNA synthesis. By subtraction hybridization of cDNAs from Nx with excess amount of those from Sham, we isolated and sequenced several genes expressed specifically in the Nx group. These included genes, which contain identical sequences with serine protease inhibitors, cytokine receptors, osteopontin as well as genes with unknown function. These genes may play important roles in the process which promotes acute glomerular damage advance to chronic and progressive glomerulosclerosis.
Insights
Researchers identified specific kidney genes linked to chronic glomerulosclerosis progression. This discovery may reveal new therapeutic targets for progressive kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Genomics
Background:
- Glomerulosclerosis can be acute and transient or chronic and progressive.
- Understanding the genetic differences between these forms is crucial for developing targeted therapies.
Purpose of the Study:
- To identify genes predominantly expressed in the kidney during chronic and progressive glomerulosclerosis.
- To differentiate these from genes involved in acute, transient glomerulonephritis.
Main Methods:
- A rat model was used, inducing progressive glomerulosclerosis via unilateral nephrectomy and anti-Thy1.1 antibody injection (Nx group).
- A control group underwent sham operation and antibody injection (Sham group).
- Messenger RNAs (mRNAs) were isolated from kidney cortex, converted to complementary DNAs (cDNAs), and analyzed using subtraction hybridization.
Main Results:
- The Nx group exhibited progressive proteinuria, mesangial expansion, and interstitial fibrosis.
- The Sham group showed transient proteinuria, mesangiolysis, and mesangial hypercellularity.
- Several specific genes, including those for serine protease inhibitors, cytokine receptors, and osteopontin, were identified in the Nx group.
Conclusions:
- The identified genes may play a critical role in the advancement of acute glomerular damage to chronic and progressive glomerulosclerosis.
- These genes represent potential therapeutic targets for managing progressive kidney disease.