Abstract
Acute glomerulonephritis can lead to chronic glomerulonephritis or resolve without permanent damage to the kidneys. Differential gene expression was studied in a model of acute and chronic glomerulonephritis to identify factors influencing the course of glomerulonephritis towards healing or chronification. One of the differentially expressed genes was identified as SCL, encoding selenocysteine lyase. Its expression was higher in acute glomerulonephritis and lower in chronic glomerulonephritis. The transcriptional regulation of SCL was studied in vitro in rat mesangial cells (MC). SCL RNA expression increased eight-fold compared to the baseline after stimulation with interleukin-1β (IL-1β) for three hours. Luciferase expression and gel shift experiments revealed an enhancer element between bp −152 and −298 of the SCL 5’-regulatory region, with protein binding to an AP-1 binding site that may be involved in the regulation of SCL-RNA in vivo in an endogenous feedback mechanism to the inflammatory reaction in acute glomerulonephritis, leading to resolution of this disease.
Key words: Selenocysteine lyase, Glomerulonephritis, Differential display, Inflammation, Mesangial cells, AP-1, Transcription
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Abbreviations used
- ATS
anti-rat thymocyte serum
- ESRD
end-stage renal disease
- IL-1β
interleukin-1β
- LUC
luciferase
- MC
mesangial cells
- PAS
periodic acid-Schiff
- PCR
polymerase chain reaction
- SCL
selenocysteine lyase
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