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Diabetologia

Erschienen in:

01.03.2012 | Article

Elevated levels of renal and circulating Nop-7-associated 2 (NSA2) in rat and mouse models of diabetes, in mesangial cells in vitro and in patients with diabetic nephropathy

verfasst von: R. Shahni, L. Gnudi, A. King, P. Jones, A. N. Malik

Erschienen in: Diabetologia | Ausgabe 3/2012

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Abstract

Aims/hypothesis

We previously found that Nop-7-associated 2 (NSA2), which is involved in ribosomal biogenesis in yeast and is a putative cell cycle regulator in mammalian cells, is elevated in the kidney of Goto–Kakizaki (GK) rat, a spontaneous model of type 2 diabetes. Here we tested the hypothesis that elevated NSA2 is involved in diabetic nephropathy (DN).

Methods

We examined Nsa2/NSA2 expression and NSA2 production in two rodent models of diabetes, in cultured renal glomerular cells, and in diabetic patients with and without nephropathy. Patients with nephropathy who had a history of albuminuria were further divided as responders (DN-NA; DN patients normoalbuminuric at the time of this study with a history of albuminuria) and non-responders (DN-A; diabetic nephropathy patients with albuminuria) to current treatment for albuminuria.

Results

Renal Nsa2/NSA2 mRNA increased in tandem with hyperglycaemia in GK rats, in a streptozotocin-induced mouse model of diabetes, and in human mesangial cells (HMCs) grown in high glucose (p < 0.05). In the mouse model of diabetes, hyperglycaemia resulted in increased Nsa2 expression and NSA2 levels in tubular and glomerular cells and in circulating cells; this increase was normalised by diabetes treatment. Circulating NSA2 mRNA levels were elevated in patients with DN independently of body weight (BMI), glycaemic (HbA_1c) and haemodynamic (blood pressure) control, and showed an inverse correlation with renal function (GFR, p < 0.05). NSA2 levels were the only variable that showed a significant difference between patients with albuminuria (DN-A) compared with non-albuminuric patients (DN-NA) and diabetic controls (p < 0.05), this increase being independent of all other variables, including GFR.

Conclusion

We show for the first time that renal and circulating NSA2/NSA2 levels are increased in hyperglycaemia in experimental models of diabetes, and that circulating NSA2 is elevated in DN patients with albuminuria. Further studies will be required to assess whether NSA2 plays a role in the pathogenesis of DN.

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Schena FB, Gesualdo (2005) Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol 16:S30–S33PubMedCrossRef

Perkins BA, Ficociello LH, Ostrander BE et al (2007) Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes. J Am Soc Nephrol 18:1353–1361PubMedCrossRef

Viberti GC, Bilous RW, Mackintosh D, Bending JJ, Keen H (1983) Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes. BMJ (Clin Res Ed) 286:598–602CrossRef

Genuth S (2006) Insights from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study on the use of intensive glycemic treatment to reduce the risk of complications of type 1 diabetes. Endocr Pract 1:34–41

The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986CrossRef

UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853CrossRef

Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 4:813–820CrossRef

Sheetz MJ, King GL (2002) Molecular understanding of hyperglycemia’s adverse effects for diabetic complications. JAMA 27:2579–2588CrossRef

Murphy M, Crean J, Brazil DP et al (2008) Regulation and consequences of differential gene expression in diabetic kidney disease. Biochem Soc Trans 36:941–945PubMedCrossRef

10.

Page RA, Morris CA, Williams CJ, Von RC, Malik AN (1997) Isolation of diabetes-associated kidney genes using differential display. Biochem Biophys Res Commun 232:49–53PubMedCrossRef

11.

Page RA, Malik AN (2003) Elevated levels of beta defensin-1 mRNA in diabetic kidneys of GK rats. Biochem Biophys Res Commum 310:513–521CrossRef

12.

Cohen CD, Lindenmeyer MT, Eichinger F et al (2008) Improved elucidation of biological processes linked to diabetic nephropathy by single probe-based microarray data analysis. PLoS One 13:e2937CrossRef

13.

Malik AN, Rossios C, Al-Kafaji G, Shah A, Page RA (2007) Glucose regulation of CDK7, a putative thiol related gene, in experimental diabetic nephropathy. Biochem Biophys Res Commun 25:237–244CrossRef

14.

Malik AN, Al-Kafaji G (2007) Glucose regulation of β-defensin 1 mRNA in human renal cells. Biochem Biophys Res Commun 353:318–323PubMedCrossRef

15.

Al-Kafaji G, Malik AN (2010) Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells. Biochem Biophys Res Commun 391:1585–1591PubMedCrossRef

16.

Lebreton A, Saveanu C, Decourty L, Jacquier A, Fromont-Racine M (2006) NSA2 is an unstable, conserved factor required for the maturation of 27 SB pre-rRNAs. J Biol Chem 281:27099–27108PubMedCrossRef

17.

Scherl A, Coute Y, Deon C et al (2002) Functional proteomic analysis of human nucleolus. Mol Biol Cell 13:4100–4109PubMedCrossRef

18.

Andersen JS, Lam YW, Leung AK et al (2005) Nucleolar proteome dynamics. Nature 433:77–83PubMedCrossRef

19.

Wu X, Ivanova G, Merup M et al (1999) Molecular analysis of the human chromosome 5q13.3 region in patients with hairy cell leukemia and identification of tumor suppressor gene candidates. Genomics 60:161–171PubMedCrossRef

20.

Zhang H, Ma X, Shi T, Song Q, Zhao H, Ma D (2010) NSA2, a novel nucleolus protein regulates cell proliferation and cell cycle. Biochem Biophys Res Commun 391:651–658PubMedCrossRef

21.

Goto Y, Kakizaki M (1981) The spontaneous diabetes rat: a model of non-insulin-dependent diabetes mellitus. Pro Japan Acad 57:381–384CrossRef

22.

King AJ, Fernandes JR, Hollister-Lock J, Nienaber CE, Bonner-Weir S, Weir GC (2007) Normal relationship of beta and non-beta-cells not needed for successful islet transplantation. Diabetes 56:2312–2318

23.

Stoves J, Lindley EJ, Barnfield MC, Burniston MT, Newstead CG (2002) MDRD equation estimates of glomerular filtration rate in potential living kidney donors and renal transplant recipients with impaired graft function. Nephrol Dial Transplant 17:2036–2037PubMedCrossRef

24.

Harnpicharnchai P, Jakovljevic J, Horsey E et al (2001) Composition and functional characterization of yeast 66S ribosome assembly intermediates. Mol Cell 8:505–515PubMedCrossRef

25.

Kanwar YS, Sun L, Xie P, Liu FY, Chen S (2011) A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol 6:395–423PubMedCrossRef

26.

Lebreton A, Rousselle JC, Lenormand P et al (2008) 60S ribosomal subunit assembly dynamics defined by semi-quantitative mass spectrometry of purified complexes. Nucleic Acids Res 36:4988–4999PubMedCrossRef

27.

Asahara S, Matsuda T, Kido Y, Kasuga M (2009) Increased ribosomal biogenesis induces pancreatic beta cell failure in mice model of type 2 diabetes. Biochem Biophys Res Commun 381:367–371PubMedCrossRef

28.

Mariappan MM, D’Silva K, Lee MJ et al (2011) Ribosomal biogenesis induction by high glucose requires activation of upstream binding factor in kidney glomerular epithelial cells. Am J Physiol Renal Physiol 300:F219–F230PubMedCrossRef

29.

Inagi R (2009) Endoplasmic reticulum stress in the kidney as a novel mediator of kidney injury. Nephron Exp Nephrol 112:e1–e9PubMedCrossRef

30.

Glassock RJ (2010) Is the presence of microalbuminuria a relevant marker of kidney disease? Curr Hypertens Rep 12:364–368PubMedCrossRef

31.

Matheson A, Willcox MD, Flanagan J, Walsh BJ (2010) Urinary biomarkers involved in type 2 diabetes: a review. Diabetes Metab Res Rev 26:150–171PubMedCrossRef

32.

Pucci L, Triscornia S, Lucchesi D et al (2007) Cystatin C and estimates of renal function: searching for a better measure of kidney function in diabetic patients. Clin Chem 53:480–488PubMedCrossRef

33.

Rigalleau V, Beauvieux MC, Le Moigne F et al (2008) Cystatin C improves the diagnosis and stratification of chronic kidney disease, and the estimation of glomerular filtration rate in diabetes. Diabetes Metab 34:482–489PubMedCrossRef

34.

Oddoze C, Morange S, Portugal H, Berland Y, Dussol B (2001) Cystatin C is not more sensitive than creatinine for detecting early renal impairment in patients with diabetes. Am J Kidney Dis 38:310–316PubMedCrossRef

35.

Jeon YK, Kim MR, Huh JE et al (2011) Cystatin C as an early biomarker of nephropathy in patients with type 2 diabetes. J Korean Med Sci 26:258–263PubMedCrossRef

36.

Kamijo-Ikemori A, Sugaya T, Yasuda T et al (2011) Clinical significance of urinary liver-type fatty acid-binding protein in diabetic nephropathy of type 2 diabetic patients. Diabetes Care 34:691–696PubMedCrossRef

37.

Okada H, Kikuta HT, Kobayashi T et al (2000) Connective tissue growth factor expressed in tubular epithelium plays a pivotal role in renal fibrogenesis. J Am Soc Nephrol 16:133–143CrossRef

38.

Nguyen TQ, Tarnow L, Jorsal A et al (2008) Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy. Diabetes Care 31:1177–1182PubMedCrossRef

Titel: Elevated levels of renal and circulating Nop-7-associated 2 (NSA2) in rat and mouse models of diabetes, in mesangial cells in vitro and in patients with diabetic nephropathy
verfasst von: R. Shahni
L. Gnudi
A. King
P. Jones
A. N. Malik
Publikationsdatum: 01.03.2012
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 3/2012
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2373-4

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Elevated levels of renal and circulating Nop-7-associated 2 (NSA2) in rat and mouse models of diabetes, in mesangial cells in vitro and in patients with diabetic nephropathy

Abstract

Aims/hypothesis

Methods

Results

Conclusion

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