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Expression of JAKs/STATs pathway molecules in rat model of rapid focal segmental glomerulosclerosis

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Abstract

The objective of this study was to investigate the role of the Janus kinase–signal transducers and activators of transcription (JAKs/STATs) pathway in focal segmental glomerulosclerosis. Sixty specific pathogen-free male Wistar rats were randomly divided into two groups: a model group (MG) and a control group (CG). In the MG group, nephropathy was induced by unilateral nephrectomy and a single tail vein injection of adriamycin (5 mg/kg). Ten rats were sacrificed every 2 weeks in each group. The expressions of smooth muscle alpha actin (α-SMA), collagen (COL)-IV, STAT1, and STAT3 were examined using histochemical techniques, and Western blotting was used to examine the protein levels of STAT1, STAT3, phosphorylated (P)-STAT1, P-STAT3, and transforming growth factor β1 (TGFβ1). The expressions of JAK1, JAK2, STAT1, STAT3, suppressors of cytokine signaling (SOCS)1, SOCS3, protein inhibitors of activated STAT (PIAS)1, and PIAS3 were also measured by real-time quantitative reverse transcriptase-PCR. A steady and significant increase in the expressions of α-SMA, COL-IV and TGFβ1 were observed in MG rats over the whole experimental course. Increased STAT1 and P-STAT1 levels in MG rats were observed by week 6, whereas increased levels of STAT3 and P-STAT3 were noted by week 2. At the mRNA levels, JAK1, STAT1, and PIAS1 were significantly increased in MG rats in week 2, whereas JAK2 mRNA showed a significant decrease by weeks 2 and 4, followed by an significant increase in week 6. Significantly increased STAT3 levels were noted in week 2, followed by a steady and significant decrease in weeks 4 and 6. Significantly reduced levels of SOCS1, SOCS3, and PIAS3 mRNA were noted at all time points. We conclude that the JAKs/STATs signaling pathway may play an important role in the pathological process of rapid focal segmental glomerulosclerosis in the rat model.

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References

  1. Cattran DC, Rao P (1998) Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. Am J Kidney Dis 32:72–79

    Article  CAS  Google Scholar 

  2. Boyer O, Moulder JK, Somers MJ (2007) Focal and segmental glomerulosclerosis in children: a longitudinal assessment. Pediatr Nephrol 22:1159–1166

    Article  Google Scholar 

  3. Hogg R, Middleton J, Vehaskari VM (2007) Focal segmental glomerulosclerosis—epidemiology aspects in children and adults. Pediatr Nephrol 22:183–186

    Article  Google Scholar 

  4. Ichikawa I, Fogo A (1996) Focal segmental glomerulosclerosis. Pediatr Nephrol 10:374–391

    Article  CAS  Google Scholar 

  5. Shiiki H, Dohi K (2000) Primary focal segmental glomerulosclerosis: clinical course, predictors of renal outcome and treatment. Intern Med 39:606–611

    Article  CAS  Google Scholar 

  6. Schlondorff D, Nelson PJ, Luckow B, Banas B (1997) Chemokines and renal disease. Kidney Int 51:610–621

    Article  CAS  Google Scholar 

  7. Brabcova I, Kotsch K, Hribova P, Louzecká A, Bartosová K, Hyklová K, Lácha J, Volk HD, Viklický O (2007) Intrarenal gene expression of proinflammatory chemokines and cytokines in chronic proteinuric glomerulopathies. Physiol Res 56:221–226

    CAS  PubMed  Google Scholar 

  8. Mezzano SA, Droguett MA, Burgos ME, Ardiles LG, Aros CA, Caorsi I, Egido J (2000) Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human membranous nephropathy. Kidney Int 57:147–158

    Article  CAS  Google Scholar 

  9. Chatterjee-Kishore M, van den Akker F, Stark GR (2000) Association of STATs with relatives and friends. Trends Cell Biol 10:106–111

    Article  CAS  Google Scholar 

  10. Leaman DW, Leung S, Li X, Stark GI (1996) Regulation of STAT-dependent pathways by growth factors and cytokines. FASEB J 10:1578–1588

    Article  CAS  Google Scholar 

  11. Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, Shuai K (1997) Specific inhibition of Stat3 signal transduction by PIAS3. Science 278:1803–1805

    Article  CAS  Google Scholar 

  12. Liu B, Liao J, Rao X, Kushner SA, Chung CD, Chang DD, Shuai K (1998) Inhibition of Stat1-mediated gene activation by PIAS1. Proc Natl Acad Sci USA 95:10626–10631

    Article  CAS  Google Scholar 

  13. Shuai K (2006) Regulation of cytokine signaling pathways by PIAS proteins. Cell Res 16:196–202

    Article  CAS  Google Scholar 

  14. Wormald S, Hilton DJ (2004) Inhibitors of cytokine signal transduction. J Biol Chem 279:821–824

    Article  CAS  Google Scholar 

  15. Tan JC, Rabkin R (2005) Suppressors of cytokine signaling in health and disease. Pediatr Nephrol 20:567–575

    Article  Google Scholar 

  16. Cooney RN (2002) Suppressors of cytokine signaling (SOCS): inhibitors of the JAK/STAT pathway. Shock 17:83–90

    Article  Google Scholar 

  17. Kile BT, Alexander WS (2001) The suppressors of cytokine signalling (SOCS). Cell Mol Life Sci 58:1627–1635

    Article  CAS  Google Scholar 

  18. Marrero MB, Banes-Berceli AK, Stern DM, Stern DM, Eaton DC (2006) Role of the JAK/STAT signaling pathway in diabetic nephropathy. Am J Physiol 290:F762–F768

    CAS  Google Scholar 

  19. Martinez-Lostao L, Ordi-Ros J, Balada E, Segarra-Medrano A, Majó-Masferrer J, Labrador-Horrillo M, Vilardell-Tarrés M (2007) Activation of the signal transducer and activator of transcription-1 in diffuse proliferative lupus nephritis. Lupus 16:483–488

    Article  CAS  Google Scholar 

  20. Li R, Yang N, Zhang L, Huang Y, Zhang R, Wang F, Luo M, Liang Y, Yu X (2007) Inhibition of Jak/STAT signaling ameliorates mice experimental nephrotic syndrome. Am J Nephrol 27:580–589

    Article  CAS  Google Scholar 

  21. Shi YH, Zhao S, Wang C, Li Y, Duan HJ (2007) Fluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions. Acta Pharmacol Sin 28:1938–1946

    Article  CAS  Google Scholar 

  22. Grond J, Weening JJ, van Goor H, Elema JD (1988) Application of puromycin aminonucleoside and adriamycin to induce chronic renal failure in the rat. Contrib Nephrol 60:83–93

    Article  CAS  Google Scholar 

  23. Okuda S, Oh Y, Tsuruda H, Onoyama K, Fujimi S, Fujishima M (1986) Adriamycin-induced nephropathy as a model of chronic progressive glomerular disease. Kidney Int 29:502–510

    Article  CAS  Google Scholar 

  24. Raij L, Azar S, Keane W (1984) Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats. Kidney Int 26:137–143

    Article  CAS  Google Scholar 

  25. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  Google Scholar 

  26. Shankland SJ (2006) The podocyte’s response to injury: role in proteinuria and glomerulosclerosis. Kidney Int 69:2131–2147

    Article  CAS  Google Scholar 

  27. Kim HS, Lee MS (2007) STAT1 as a key modulator of cell death. Cell Signal 19:454–465

    Article  CAS  Google Scholar 

  28. Bromberg JF (2001) Activation of STAT proteins and growth control. Bioessays 23:161–169

    Article  CAS  Google Scholar 

  29. Battle TE, Frank DA (2002) The role of STATs in apoptosis. Curr Mol Med 2:381–392

    Article  CAS  Google Scholar 

  30. Eddy AA (1994) Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions. J Am Soc Nephrol 5:1273–1287

    CAS  PubMed  Google Scholar 

  31. Ivashkiv LB (2000) Jak-STAT signaling pathways in cells of the immune system. Rev Immunogenet 2:220–230

    CAS  PubMed  Google Scholar 

  32. Mu W, Ouyang X, Agarwal A, Zhang L, Long DA, Cruz PE, Roncal CA, Glushakova OY, Chiodo VA, Atkinson MA, Hauswirth WW, Flotte TR, Rodriguez-Iturbe B, Johnson RJ (2005) IL-10 suppresses chemokines, inflammation, and fibrosis in a model of chronic renal disease. J Am Soc Nephrol 16:3651–3660

    Article  CAS  Google Scholar 

  33. Alexander WS (2002) Suppressors of cytokine signalling (SOCS) in the immune system. Nat Rev 2:410–416

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, The First Hospital of Lanzhou University, Lanzhou, China

    Yaojun Liang, Yu Jin & Yuning Li

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  1. Yaojun Liang
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  2. Yu Jin
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  3. Yuning Li
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Correspondence to Yu Jin.

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Liang, Y., Jin, Y. & Li, Y. Expression of JAKs/STATs pathway molecules in rat model of rapid focal segmental glomerulosclerosis. Pediatr Nephrol 24, 1661–1671 (2009). https://doi.org/10.1007/s00467-009-1163-4

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  • DOI: https://doi.org/10.1007/s00467-009-1163-4

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