Ekspresi dan Aktivasi Reseptor Glukokortikoid serta Ekspresi Heat Shock Protein- 90 pada Sel Limfosit Penderita Sindrom Nefrotik Idiopatik


  • Khairiyadi Khairiyadi RSUD Ulin Balikpapan
  • Krisni Subandiyah Departemen Ilmu Kesehatan Anak RSSA/Fakultas Kedokteran Universitas Brawijaya
  • Loeki Enggar Fitri Departemen Parasitologi Fakultas Kedokteran Universitas Brawijaya




Glucocorticoid receptors (GR) have an important role in the resistance of steroid therapy . Previous studies showed  significant  difference  activation  and  expression  of  GR  between  Steroid  Resistant  Nephrotic Syndrome (SRNS) and Steroid Sensitive Nephrotic Syndrome (SSNS), however the other studies showed contrastive result. Previous studies also revealed Hsp-90 had an important  role in  GR activation. The aim of this study was to determine the differences expression and activation of GR and also Hsp-90 expression in lymphocytes  cytoplasm  and  nucleus  between  SRNS  and  SSNS  patients.  A  Cross-sectional  study  was conducted  to  40  children  (20  SRNS  and  20  SSNS  patients).  Double  stainning  immunocytochemistry  of lymphocytes  was  performed.  The  GR  expression  and  activation  were  determined  by  counting  amount  of lymphocytes  that  express GR and Hsp-90 among 200 under light  microscope with 1000x magnification. The differences  of  activation  and  activation  of  GR  and  Hsp-90  in  cytoplasm  and  nucleus  were  analyzed  with independent t-test and the correlation was analyzed with Pearson correlation.


Download data is not yet available.


Orth SR, Eberhard R. The nephrotic syndromes. NEJM.1998;338:1202-11.

Bagadasarova IV, Ivanov DD, Afanas'eva VV. The morphofunctionalcharacteristics of the blood Iymphocytes in steroid sensitive and steroid resistant glomerulonefritis. Arkh Pathol. 1991;53,28-32.

Rio MD, Frederick K. Evaluation and management of steroidunresponsivenephrotic syndrome current opinion in pediatrics .NEJM.2008;20:151-6.

Bagga A, Mantan M. Neprotic Syndrome in Children. Indian J Med Resp.2005;122:13-28.

Alatas H, Taralan T, Partini PT, Sudung OP. Konsensus Tatalaksana Sindrom Nefrotik Pada Anak. Ikatan Dokter Anak Indonesia.Jakarta. 2005

Lee KW, Mak R. Update Review of Therapeutic Regimens for Steroid Resistant Idiopathic Nephrotic Syndrome. HK J Paediatr. 2000;5:70-5.

Grenert JP ,Sulivan WP, Fadden P, et al. The amino-terminal domain heat shock protein 90 (hsp90) that bind geldanamycin is an ATP/ADP switch domain that regulates Hsp90 conformation. J Bio Chem.1997;272:23843-5

Yu Z, Ding J, Huang J, Yao Y, et al. Mutations in NPHS2 in sporadic steroid-resistant nephrotic syndrome in Chinese children. Nephrol Dial Transplant.2005;20:9028.

Karle SM, Uetz B, Ronner V, Glaeser L, Hildebrandt F, Fuchshuber A. Novel mutations in NPHS2 detected in both familial and sporadic steroid-resistant nephrotic syndrome. J Am Soc Nephrol.2002;13:38893.

Kang K I, Xia M, Jocelyn DL, Ilham B, et al. The molecular chaperone hsp-90 can negative regulate of a glucocorticosteroid dependent promoter. ProcNatl Acd Sci USA.1999;95:1439-44.

Wasilewska A, Walentyna ZB, Tomaszewska, Ryszard W, Anna SB. Expression of glucocorticoid receptors in mononuclear cells in nephritic syndrome. Pediatr nephrol. 2003;18:778-82

Berki T, Nagy KK, Nagy G, Nemeth P. Alteration of glukokortikoid hormone therapy in remathoid arthritis. Arthritis Rheum. 2002;35:132-38

Tago K, Fujiko T, Mitsuhide N, Toshimasa Y, Kazue T. Regulation of nuclear retention of glucocorticoid receptor by Hsp90. Mol and cell Endocrinol. 2004;213:131-8

Quyang J, Tang J, Min T, Yin C, Xiaoyan L. Abnormal expression and distribution heat stroke protein 90:potential etiologic immunoendocrinemechanism of glucocorticoid resistance inidiophatic nephritic syndrome. J neprol Dial. 2006;34:496-500.

Zhang X, Abbot FG, Thomas V. Heat shock protein is essensial molecular chaperone for nuclear transport of glucocorticoid receptor. IOVS. 2006;47:700-8.

Hodson EM, Habashy D, Craig JC. Intervention for idiophatic steroidresitant nephritic syndrome In children. The Cochrane Review Journal. 2007;6:267-72.

Hodson EM, John FK, Narelle SW, Jonathan CC. Corticosteroid therapy in nephritic syndrome: a meta-analysis of randomized controlled trials. Arch Dis Child. 2000;83:45-51.

Nicela BM, CidlowskiA. Mechanisms of glucocorticoid Receptor action in noninflamatory and inflammatory cells. Proc Am Thorac Soc. 2004;1:239-46.

Burnstein KL, Cidlowski JA. The Downside of glucocorticoid receptor regulation. Moll Cell Endocrinol. 1992;8:C61-C68.

Han SH, Park SY, Li J, Kwak SJ, Jung DS, Choi HY. Glomerular glucocorticoid receptor expression is reduced in late responders to steroids in adult-onset minimal change disease. Nephrol Dial Transplant. 2008;23:169175.

Haack D, Schrer K, Taucher A, Vesse P. Glucocorticoid receptors in idiopathic nephritic syndrome. Pediat Nephrol. 1999;13:653-56.

Carrigan A, Walther RF, Salem HA, Wu D, Atlas E, Lefebvre Y A. An Active Nuclear Retention Signal in the Glucocorticoid Receptor Functions as a Strong Inducer of Transcriptional Activation. The Jour Of Biol Chem. 2007;282(15):1096371

Charmandari E, George PC, Takamasa I, et al. The human glucocorticoid Receptor (hGR) isoform suppresses the transcriptional activity of hGR by interfering with formation of active coactivator complexe. Mol Endocrinol. 2005;19:52-64.

Elbi C, Dawn AW, Guilermo R, et al. Molecular Chaperons function as steroid receptor nuclear mobility factors. PNAS. 2004;101:2877-881.

Gross KL, Lu NZ, Cidlowski JA. Molecular mechanisms regulating glucocorticoid sensitivity and resistance. Mol & Cell Endocrinol. 2008;300:716.

Young JC, Muorefi I, Hard FU. Hsp90 : a specialized but essensial protein-folding tool. J cell Biology.2001;152(2):267-73.

Czar MJ, Galigniana MD, Silvetstein AM, Pratt WB..Geldanamycin, heat shock protein 90-binding benzoqui none ansamysin, inhibits steroid-dependent translocation of glucocortcoid receptor from the cytoplasm to nucleus. Biochem. 1997;36:7776-85.

Nollen AAE, Morimoto RI. Chaperoning signaling pathways: molecular chaperones as stress-sensing 'heat shock' proteins. J of Cell Scie.

Gulati S, Pokharial S, Sharma RK, et al. Pulse cyclophosphami de therapy in frequently relapsing nephritic syndrome. Nephrol Dial Transplant.2005;16:2013-2017.

Jha V, Ganguli A, Saha TK,et al. A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy. J Am Soc Nephro . 2007;18:1899-1904.






Research Article