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Human proximal tubular cell responses to angiotensin II analyzed using DNA microarray
Branko Braam1, Pat Allen, Ed Benes
1Nephrology Section, and Tulane Environmental Astrobiology Center, New Orleans, LA, USA. g.b.braam@azu.nl
European Journal of Pharmacology
|March 7, 2003
Summary
Angiotensin II directly influences human kidney tubular cells, altering gene expression. This peptide rapidly activates transcription factors and antioxidant genes, indicating its direct role in cellular regulation.
Area of Science:
- Nephrology
- Molecular Biology
- Genomics
Background:
- Angiotensin II has complex effects on kidney proximal tubular cells.
- Understanding direct cellular responses is crucial for kidney physiology.
Purpose of the Study:
- To investigate the direct effects of Angiotensin II on proximal tubular cell gene expression.
- To identify specific cellular pathways regulated by Angiotensin II.
Main Methods:
- Human proximal tubular cells were exposed to varying concentrations of Angiotensin II (10 and 100 nM).
- Gene expression changes were analyzed using custom DNA microarrays.
- Western blot confirmed the presence of the Angiotensin type 1 receptor.
Main Results:
- Angiotensin II significantly altered the expression of transcription factors, including hepatocyte nuclear factor 3 family and E2F genes.
- Expression of interferon regulatory factors (IRF1, IRF5) and antioxidant genes was induced.
- Hormone and hormone receptor genes also showed altered expression.
Conclusions:
- Angiotensin II directly initiates a cascade of gene expression events in proximal tubular cells.
- The peptide rapidly activates transcription factors and antioxidant pathways.
- These findings highlight Angiotensin II's direct regulatory role in kidney tubular cells.