Glucocorticoid receptor auto-upregulation and its relation with glucocorticoid sensitivity in idiopathic nephrotic syndrome.
BACKGROUND
Resistance to glucocorticoid (GC) treatment is a significant clinical problem in many diseases. Most effects of GC are mediated by glucocorticoid receptor (GR). Multiple promoters have been found in GR gene, which results in different exons 1 s. In human leukemia cell lines, GC response is thought to be related with promoter usage and auto-upregulation of GR. In this study, we investigated whether GR could be auto-induced in peripheral blood mononuclear cells (PBMCs) and whether an inability to upregulate the GR is related with GC resistance in idiopathic nephrotic syndrome (INS).


METHODS
Reverse transcription-PCR was applied to measure the mRNA expression of GR transcripts (GR exons 1A, 1B, 1C, and GR), and real-time PCR was used to confirm these results. GR protein expression was analyzed by Western blot.


RESULTS
Following GC treatment, both GR exon 1A and GR in PBMCs were increased in vitro, while GR exons 1B and 1C showed no significant changes. In patients with INS, the glucocorticoid-sensitive group expressed more GR exon 1A and less GR exon 1C than the glucocorticoid-resistant group, but the total GR showed no significant difference.


CONCLUSIONS
GR is auto-induced in PBMCs in vitro and GR promoter 1A is involved in this mechanism; however the auto-upregulation of GR is not related with glucocorticoid response in patients with INS.
Chen
Peisong
P
Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong, China.
Jiang
Tang
T
Ouyang
Juan
J
Cui
Yingpeng
Y
D000328:Adult; D015153:Blotting, Western; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009402:Nephrosis, Lipoid / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013053:Spectrophotometry; D015854:Up-Regulation
D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid