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Published in: International Urology and Nephrology 2/2010

01-06-2010 | Nephrology - Original Paper

Association of macroalbuminuria with oxidized LDL and TGF-β in type 2 diabetic patients: a case–control study

Authors: Manouchehr Nakhjavani, Alireza Esteghamati, Omid Khalilzadeh, Firouzeh Asgarani, Nasrin Mansournia, Mehrshad Abbasi

Published in: International Urology and Nephrology | Issue 2/2010

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Abstract

The pathogenesis of diabetic nephropathy, mainly characterized by macroalbuminuria, is still poorly understood, but it is reported that transforming growth factor-β (TGF-β) plays a key role. In vitro evidence suggests that administration of oxidized LDL (ox-LDL) can lead to upregulation of TGF-β by human glomerular mesangial cells. This study aimed to evaluate the association between macroalbuminuria, ox-LDL, and TGF-β in diabetic patients. A total of 77 type 2 diabetic patients with macroalbuminuria (albumin excretion rate: AER ≥ 300 mg/24 h) and 66 patients with normoalbuminuria (AER ≤ 30 mg/24 h) were recruited. Fasting blood samples were obtained and serum levels of ox-LDL and TGF-β were determined. Ox-LDL and TGF-β were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria (98.93 ± 3.99 vs. 72.45 ± 2.48 U/l; P < 0.001 and 6.46 ± 0.74 vs. 2.49 ± 0.39 ng/ml; P < 0.001, respectively). In patients with macroalbuminuria, there was a significant correlation between Ox-LDL and TGF-β (r = 0.376; P < 0.01). AER was significantly correlated to ox-LDL (r = 0.302; P < 0.05) and TGF-β (r = 0.306; P < 0.05) in macroalbuminuric patients. This association remained significant after adjustment for potential confounders. Adjustment for TGF-β (ox-LDL), attenuated the association of ox-LDL (TGF-β) with AER. In conclusion, this study demonstrated the association of TGF-β and ox-LDL with albuminuria in macroalbuminuric type 2 diabetic patients, and suggested that this relationship is highly mediated through the correlation between TGF-β and ox-LDL.
Literature
1.
go back to reference Molitch ME, DeFronzo RA, Franz MJ et al (2004) Nephropathy in diabetes. Diabetes Care 27(Suppl 1):S79–S83PubMed Molitch ME, DeFronzo RA, Franz MJ et al (2004) Nephropathy in diabetes. Diabetes Care 27(Suppl 1):S79–S83PubMed
2.
go back to reference Wang SN, LaPage J, Hirschberg R (2000) Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy. Kidney Int 57:1002–1014CrossRefPubMed Wang SN, LaPage J, Hirschberg R (2000) Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy. Kidney Int 57:1002–1014CrossRefPubMed
3.
go back to reference Chen S, Iglesias-de la Cruz MC, Jim B, Hong SW, Isono M, Ziyadeh FN (2003) Reversibility of established diabetic glomerulopathy by anti-TGF-beta antibodies in db/db mice. Biochem Biophys Res Commun 300:16–22CrossRefPubMed Chen S, Iglesias-de la Cruz MC, Jim B, Hong SW, Isono M, Ziyadeh FN (2003) Reversibility of established diabetic glomerulopathy by anti-TGF-beta antibodies in db/db mice. Biochem Biophys Res Commun 300:16–22CrossRefPubMed
4.
go back to reference Chen S, Hong SW, Iglesias-de la Cruz MC, Isono M, Casaretto A, Ziyadeh FN (2001) The key role of the transforming growth factor-beta system in the pathogenesis of diabetic nephropathy. Ren Fail 23:471–481CrossRefPubMed Chen S, Hong SW, Iglesias-de la Cruz MC, Isono M, Casaretto A, Ziyadeh FN (2001) The key role of the transforming growth factor-beta system in the pathogenesis of diabetic nephropathy. Ren Fail 23:471–481CrossRefPubMed
5.
go back to reference Russo LM, Osicka TM, Brammar GC, Candido R, Jerums G, Comper WD (2003) Renal processing of albumin in diabetes and hypertension in rats: possible role of TGF-beta1. Am J Nephrol 23:61–70CrossRefPubMed Russo LM, Osicka TM, Brammar GC, Candido R, Jerums G, Comper WD (2003) Renal processing of albumin in diabetes and hypertension in rats: possible role of TGF-beta1. Am J Nephrol 23:61–70CrossRefPubMed
6.
go back to reference Russo LM, del Re E, Brown D, Lin HY (2007) Evidence for a role of transforming growth factor (TGF)-beta1 in the induction of postglomerular albuminuria in diabetic nephropathy: amelioration by soluble TGF-beta type II receptor. Diabetes 56:380–388CrossRefPubMed Russo LM, del Re E, Brown D, Lin HY (2007) Evidence for a role of transforming growth factor (TGF)-beta1 in the induction of postglomerular albuminuria in diabetic nephropathy: amelioration by soluble TGF-beta type II receptor. Diabetes 56:380–388CrossRefPubMed
7.
go back to reference Rocco MV, Chen Y, Goldfarb S, Ziyadeh FN (1992) Elevated glucose stimulates TGF-beta gene expression and bioactivity in proximal tubule. Kidney Int 41:107–114CrossRefPubMed Rocco MV, Chen Y, Goldfarb S, Ziyadeh FN (1992) Elevated glucose stimulates TGF-beta gene expression and bioactivity in proximal tubule. Kidney Int 41:107–114CrossRefPubMed
8.
go back to reference Zhu Y, Usui HK, Sharma K (2007) Regulation of transforming growth factor beta in diabetic nephropathy: implications for treatment. Semin Nephrol 27:153–160CrossRefPubMed Zhu Y, Usui HK, Sharma K (2007) Regulation of transforming growth factor beta in diabetic nephropathy: implications for treatment. Semin Nephrol 27:153–160CrossRefPubMed
9.
go back to reference Song CY, Kim BC, Hong HK, Lee HS (2005) Oxidized LDL activates PAI-1 transcription through autocrine activation of TGF-beta signaling in mesangial cells. Kidney Int 67:1743–1752CrossRefPubMed Song CY, Kim BC, Hong HK, Lee HS (2005) Oxidized LDL activates PAI-1 transcription through autocrine activation of TGF-beta signaling in mesangial cells. Kidney Int 67:1743–1752CrossRefPubMed
10.
go back to reference Lan Y, Zhou Q, Wu ZL (2004) NF-kappa B involved in transcription enhancement of TGF-beta 1 induced by Ox-LDL in rat mesangial cells. Chin Med J (Engl) 117:225–230 Lan Y, Zhou Q, Wu ZL (2004) NF-kappa B involved in transcription enhancement of TGF-beta 1 induced by Ox-LDL in rat mesangial cells. Chin Med J (Engl) 117:225–230
11.
go back to reference Okada M, Takemura T, Yanagida H, Yoshioka K (2002) Response of mesangial cells to low-density lipoprotein and angiotensin II in diabetic (OLETF) rats. Kidney Int 61:113–124CrossRefPubMed Okada M, Takemura T, Yanagida H, Yoshioka K (2002) Response of mesangial cells to low-density lipoprotein and angiotensin II in diabetic (OLETF) rats. Kidney Int 61:113–124CrossRefPubMed
12.
go back to reference Lee HS, Kim YS (1998) Identification of oxidized low density lipoprotein in human renal biopsies. Kidney Int 54:848–856CrossRefPubMed Lee HS, Kim YS (1998) Identification of oxidized low density lipoprotein in human renal biopsies. Kidney Int 54:848–856CrossRefPubMed
13.
go back to reference Takemura T, Yoshioka K, Aya N et al (1993) Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases. Kidney Int 43:918–927CrossRefPubMed Takemura T, Yoshioka K, Aya N et al (1993) Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases. Kidney Int 43:918–927CrossRefPubMed
14.
go back to reference Grone HJ, Walli AK, Grone E, Kramer A, Clemens MR, Seidel D (1990) Receptor mediated uptake of apo B and apo E rich lipoproteins by human glomerular epithelial cells. Kidney Int 37:1449–1459CrossRefPubMed Grone HJ, Walli AK, Grone E, Kramer A, Clemens MR, Seidel D (1990) Receptor mediated uptake of apo B and apo E rich lipoproteins by human glomerular epithelial cells. Kidney Int 37:1449–1459CrossRefPubMed
15.
go back to reference Song CY, Kim BC, Lee HS (2008) Lovastatin inhibits oxidized low-density lipoprotein-induced plasminogen activator inhibitor and transforming growth factor-beta1 expression via a decrease in Ras/extracellular signal-regulated kinase activity in mesangial cells. Transl Res 151:27–35CrossRefPubMed Song CY, Kim BC, Lee HS (2008) Lovastatin inhibits oxidized low-density lipoprotein-induced plasminogen activator inhibitor and transforming growth factor-beta1 expression via a decrease in Ras/extracellular signal-regulated kinase activity in mesangial cells. Transl Res 151:27–35CrossRefPubMed
16.
go back to reference Lee HS, Song CY (2009) Oxidized low-density lipoprotein and oxidative stress in the development of glomerulosclerosis. Am J Nephrol 29:62–70CrossRefPubMed Lee HS, Song CY (2009) Oxidized low-density lipoprotein and oxidative stress in the development of glomerulosclerosis. Am J Nephrol 29:62–70CrossRefPubMed
17.
go back to reference American Diabetes Association (2008) Diagnosis and classification of diabetes mellitus. Diabetes Care 31(Suppl 1):S55–S60CrossRef American Diabetes Association (2008) Diagnosis and classification of diabetes mellitus. Diabetes Care 31(Suppl 1):S55–S60CrossRef
18.
go back to reference Shin GT, Kim SJ, Ma KA, Kim HS, Kim D (2000) ACE inhibitors attenuate expression of renal transforming growth factor-beta1 in humans. Am J Kidney Dis 36:894–902CrossRefPubMed Shin GT, Kim SJ, Ma KA, Kim HS, Kim D (2000) ACE inhibitors attenuate expression of renal transforming growth factor-beta1 in humans. Am J Kidney Dis 36:894–902CrossRefPubMed
19.
go back to reference Langham RG, Kelly DJ, Gow RM et al (2006) Transforming growth factor-beta in human diabetic nephropathy: effects of ACE inhibition. Diabetes Care 29:2670–2675CrossRefPubMed Langham RG, Kelly DJ, Gow RM et al (2006) Transforming growth factor-beta in human diabetic nephropathy: effects of ACE inhibition. Diabetes Care 29:2670–2675CrossRefPubMed
20.
go back to reference Chen S, Jim B, Ziyadeh FN (2003) Diabetic nephropathy and transforming growth factor-beta: transforming our view of glomerulosclerosis and fibrosis build-up. Semin Nephrol 23:532–543CrossRefPubMed Chen S, Jim B, Ziyadeh FN (2003) Diabetic nephropathy and transforming growth factor-beta: transforming our view of glomerulosclerosis and fibrosis build-up. Semin Nephrol 23:532–543CrossRefPubMed
21.
go back to reference Gekle M, Knaus P, Nielsen R et al (2003) Transforming growth factor-beta 1 reduces megalin- and cubilin-mediated endocytosis of albumin in proximal-tubule-derived opossum kidney cells. J Physiol 552:471–481CrossRefPubMed Gekle M, Knaus P, Nielsen R et al (2003) Transforming growth factor-beta 1 reduces megalin- and cubilin-mediated endocytosis of albumin in proximal-tubule-derived opossum kidney cells. J Physiol 552:471–481CrossRefPubMed
22.
go back to reference Wolf G, Chen S, Ziyadeh FN (2005) From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy. Diabetes 54:1626–1634CrossRefPubMed Wolf G, Chen S, Ziyadeh FN (2005) From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy. Diabetes 54:1626–1634CrossRefPubMed
23.
go back to reference Viswanathan V, Snehalatha C, Nair MB, Kumutha R, Ramachandran A (2005) Levels of transforming growth factor beta 1 in south Indian type 2 diabetic subjects. Diabetes Metab Res Rev 21:276–280CrossRefPubMed Viswanathan V, Snehalatha C, Nair MB, Kumutha R, Ramachandran A (2005) Levels of transforming growth factor beta 1 in south Indian type 2 diabetic subjects. Diabetes Metab Res Rev 21:276–280CrossRefPubMed
24.
go back to reference Nakhjavani M, Esteghamati A, Asgarani F, Khalilzadeh O, Nikzamir A, Safari R (2009) Association of oxidized low-density lipoprotein (LDL) and transforming growth factor-beta (TGF-β) in type 2 diabetic patients: a cross-sectional study. Transl Res 153:86–90CrossRefPubMed Nakhjavani M, Esteghamati A, Asgarani F, Khalilzadeh O, Nikzamir A, Safari R (2009) Association of oxidized low-density lipoprotein (LDL) and transforming growth factor-beta (TGF-β) in type 2 diabetic patients: a cross-sectional study. Transl Res 153:86–90CrossRefPubMed
25.
go back to reference Hellmich B, Schellner M, Schatz H, Pfeiffer A (2000) Activation of transforming growth factor-beta 1 in diabetic kidney disease. Metabolism 49:353–359CrossRefPubMed Hellmich B, Schellner M, Schatz H, Pfeiffer A (2000) Activation of transforming growth factor-beta 1 in diabetic kidney disease. Metabolism 49:353–359CrossRefPubMed
26.
go back to reference Wang H, Deng H, Liu W (2002) The effects of paraoxonase-1 and oxidized low density lipoprotein on nephropathy in type-2 diabetes mellitus. Zhonghua Nei Ke Za Zhi 41:179–182PubMed Wang H, Deng H, Liu W (2002) The effects of paraoxonase-1 and oxidized low density lipoprotein on nephropathy in type-2 diabetes mellitus. Zhonghua Nei Ke Za Zhi 41:179–182PubMed
27.
go back to reference Ujihara N, Sakka Y, Takeda M et al (2002) Association between plasma oxidized low-density lipoprotein and diabetic nephropathy. Diabetes Res Clin Pract 58:109–114CrossRefPubMed Ujihara N, Sakka Y, Takeda M et al (2002) Association between plasma oxidized low-density lipoprotein and diabetic nephropathy. Diabetes Res Clin Pract 58:109–114CrossRefPubMed
28.
go back to reference Atchley DH, Lopes-Virella MF, Zheng D, Kenny D, Virella G (2002) Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy. Diabetologia 45:1562–1571CrossRefPubMed Atchley DH, Lopes-Virella MF, Zheng D, Kenny D, Virella G (2002) Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy. Diabetologia 45:1562–1571CrossRefPubMed
29.
go back to reference Ding G, van Goor H, Ricardo SD, Orlowski JM, Diamond JR (1997) Oxidized LDL stimulates the expression of TGF-beta and fibronectin in human glomerular epithelial cells. Kidney Int 51:147–154CrossRefPubMed Ding G, van Goor H, Ricardo SD, Orlowski JM, Diamond JR (1997) Oxidized LDL stimulates the expression of TGF-beta and fibronectin in human glomerular epithelial cells. Kidney Int 51:147–154CrossRefPubMed
Metadata
Title
Association of macroalbuminuria with oxidized LDL and TGF-β in type 2 diabetic patients: a case–control study
Authors
Manouchehr Nakhjavani
Alireza Esteghamati
Omid Khalilzadeh
Firouzeh Asgarani
Nasrin Mansournia
Mehrshad Abbasi
Publication date
01-06-2010
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 2/2010
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-009-9643-9

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