Enhanced expression of selenocysteine lyase in acute glomerulonephritis and its regulation by AP-1.
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-1beta (IL-1beta) 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.
Jafari
Claudia
C
Zentrum für Innere Medizin, III, Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Panzer
Ulf
U
Steinmetz
Oliver M
OM
Zahner
Gunther
G
Stahl
Rolf A K
RA
Harendza
Sigrid
S
D000818:Animals; D020029:Base Pairing / Q000187:drug effects; D001483:Base Sequence; D001665:Binding Sites; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005921:Glomerulonephritis / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics*; D053583:Interleukin-1beta / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008190:Lyases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018800:Thy-1 Antigens; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D053583:Interleukin-1beta; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D018808:Transcription Factor AP-1; D008190:Lyases; C034278:selenocysteine lyase