Role of the glucocorticoid receptor in the recurrence of primary nephrotic syndrome

Liang,Yumei; Chen,Yinyin; Chen,Ying; Gong,Yuting

doi:10.3892/etm.2015.2665

Role of the glucocorticoid receptor in the recurrence of primary nephrotic syndrome

Authors:
- Yumei Liang
- Yinyin Chen
- Ying Chen
- Yuting Gong
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Affiliations: Department of Nephrology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
Published online on: July 30, 2015 https://doi.org/10.3892/etm.2015.2665
Pages: 1556-1562

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Abstract

The present study aimed to investigate the changes in the expression levels of the glucocorticoid receptor (GR) and its subtypes in patients with recurrent renal syndrome. In addition, the effects of tumour necrosis factor α (TNF‑α) and a TNF‑α monoclonal antibody on these receptors in peripheral blood mononuclear cells (PBMCs) isolated from the patients was analysed. Furthermore, a new treatment method for recurrent renal syndrome was explored. The serum levels of TNF‑α in the normal (A), stable renal syndrome (B) and renal syndrome recurrence (C) groups of patients were determined by enzyme‑linked immunosorbent assay (ELISA). The mRNA and protein expression levels of GR, GRα and GRβ were determined by ELISA, western blot analysis and quantitative polymerase chain reaction in PBMC cultures from the three groups in the absence of intervention (blank control) and following stimulation with methylprednisolone, TNF‑α and/or TNF‑α monoclonal antibody. Group C exhibited higher expression levels of TNF‑α and GRβ but a lower level of GRα expression (P<0.05) compared with the other groups. Regardless of methylprednisolone intervention, the expression levels of GR and GRβ in the three groups following stimulation by TNF‑α were significantly higher compared with those in the respective blank control, whereas in group C, the GRα expression levels following TNF‑α treatment were lower compared with those in the control group (P<0.05). The treatment of group C with TNF‑α monoclonal antibodies resulted in higher GRα expression but lower GRβ expression compared with those in the blank control (P<0.05). The change in the ratios of the GR subtypes may be associated with renal syndrome recurrence. TNF‑α may be involved in renal syndrome relapse by changing the levels of GR as well as the proportion of the GR subtypes. TNF-α monoclonal antibodies may mitigate the changes in the ratios of these subtypes.

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1	Zhang HW, Wang F and Ding J: Updates on the molecular genetics of congenital nephrotic syndrome. Zhonghua Er Ke Za Zhi. 49:425–427. 2011.(In Chinese). PubMed/NCBI
2	Stahl RA, Hoxha E and Helmchen U: Membranous glomerulonephritis: better therapy with autoantibody monitoring? Dtsch Med Wochenschr. 136:1733–1737. 2011.(In German). View Article : Google Scholar : PubMed/NCBI
3	Bruneau S and Dantal J: New insights into the pathophysiology of idiopathic nephrotic syndrome. Clin Immunol. 133:13–21. 2009. View Article : Google Scholar : PubMed/NCBI
4	Bomback AS and Radhakrishnan J: Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH). Discov Med. 12:91–96. 2011.PubMed/NCBI
5	Saito T: Treatment and prognosis of idiopathic membranous nephropathy in guidelines for nephrotic syndrome. Nihon Jinzo Gakkai Shi. 53:708–712. 2011.(In Japanese). PubMed/NCBI
6	Guess A, Agrawal S, Wei CC, Ransom RF, Benndorf R and Smoyer WE: Dose- and time-dependent glucocorticoid receptor signaling in podocytes. Am J Physiol Renal Physiol. 299:F845–F853. 2010. View Article : Google Scholar : PubMed/NCBI
7	Wang L, Li Q, Wang LJ and Li X: Level of Th17 cell and CD4(+); CD25(+); Foxp3(+); regulatory T cell in peripheral blood mononuclear cells of primary nephrotic syndrome in children. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 26:783–786. 2010.(In Chinese). PubMed/NCBI
8	Farid FA, Mohammed AA, Afifi HM and Beltagi RS: Tissue factor pathway inhibitor in paediatric patients with nephrotic syndrome. SAJCH. 5:107–111. 2011.PubMed/NCBI
9	Tan Y, Yang D, Fan J and Chen Y: Elevated levels of immunoglobulin E may indicate steroid resistance or relapse in adult primary nephrotic syndrome, especially in minimal change nephrotic syndrome. J Int Med Res. 39:2307–2313. 2011. View Article : Google Scholar : PubMed/NCBI
10	Audard V, Pawlak A, Candelier M, Lang P and Sahali D: Upregulation of nuclear factor-related kappa B suggests a disorder of transcriptional regulation in minimal change nephrotic syndrome. PLoS One. 7:e305232012. View Article : Google Scholar : PubMed/NCBI
11	Caridi G, Trivelli A, SannaCherchi S, Perfumo F and Ghiggeri GM: Familial forms of nephrotic syndrome. Pediatr Nephrol. 25:241–252. 2010. View Article : Google Scholar : PubMed/NCBI
12	Elie V, Fakhoury M, Deschênes G and Jacqz-Aigrain E: Physiopathology of idiopathic nephrotic syndrome: lessons from glucocorticoids and epigenetic perspectives. Pediatr Nephrol. 27:1249–1256. 2012. View Article : Google Scholar : PubMed/NCBI
13	Segal PE and Choi MJ: Recent advances and prognosis in idiopathic membranous nephropathy. Adv Chronic Kidney Dis. 19:114–119. 2012. View Article : Google Scholar : PubMed/NCBI
14	Shalaby SA, El Idrissy HM, Safar RA and Hussein ST: Glucocorticoid receptors and the pattern of steroid response in idiopathic nephrotic syndrome. Arab J Nephrol Transplant. 5:13–17. 2012.PubMed/NCBI
15	Szilagyi K, Podracka L, Franke NE, Mojzis J and Mirossay L: A new link between steroid resistance, glucocorticoid receptor and nuclear factor kappa B p65 in idiopathic nephrotic syndrome. Neuro Endocrinol Lett. 30:629–636. 2009.PubMed/NCBI
16	Chen P, Jiang T, Ouyang J and Cui Y: Glucocorticoid receptor auto-upregulation and its relation with glucocorticoid sensitivity in idiopathic nephrotic syndrome. Int Urol Nephrol. 43:167–174. 2011. View Article : Google Scholar : PubMed/NCBI
17	Pace TW, Hu F and Miller AH: Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun. 21:9–19. 2007. View Article : Google Scholar : PubMed/NCBI
18	Wang X, Wu H, Lakdawala VS, Hu F, Hanson ND and Miller AH: Inhibition of Jun N-terminal kinase (JNK) enhances glucocorticoid receptor-mediated function in mouse hippocampal HT22 cells. Neuropsychopharmacology. 30:242–249. 2005. View Article : Google Scholar : PubMed/NCBI
19	Wang X, Wu H and Miller AH: Interleukin 1alpha (IL-1alpha) induced activation of p38 mitogen-activated protein kinase inhibits glucocorticoid receptor function. Mol Psychiatry. 9:65–75. 2004. View Article : Google Scholar : PubMed/NCBI
20	Rogatsky I and Ivashkiv LB: Glucocorticoid modulation of cytokine signaling. Tissue Antigens. 68:1–12. 2006. View Article : Google Scholar : PubMed/NCBI
21	Biola A, Lefebvre P, PerrinWolff M, Sturm M, Bertoglio J and Pallardy M: Interleukin-2 inhibits glucocorticoid receptor transcriptional activity through a mechanism involving STAT5 (signal transducer and activator of transcription 5) but not AP-1. Mol Endocrinol. 15:1062–1076. 2001. View Article : Google Scholar : PubMed/NCBI
22	Kam JC, Szefler SJ, Surs W, Sher ER and Leung DY: Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids. J Immunol. 151:3460–3466. 1993.PubMed/NCBI