The Effects of Inflammation on Lipid Accumulation in the Kidneys of Children with Primary Nephrotic Syndrome

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 2010 Nov 25

PMID 21103916

Citations 7

Authors

Gaofu Zhang

Qiu Li

Li Wang

Yaxi Chen

Wei Zhang

Haiping Yang

Affiliations

Soon will be listed here.

Abstract

This study aimed to characterize the relationship between inflammation and lipid accumulation in children with primary nephrotic syndrome (PNS). Local expression of interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), low-density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), SREBP cleavage-activating protein (SCAP), and apolipoprotein B100 (apoB100) was analyzed by immunohistochemistry in kidney tissues obtained from children with PNS. Renal histopathology was evaluated by hematoxylin and eosin and periodic acid-Schiff staining. Serum levels of IL-1β and TGF-β1 were measured by enzyme-linked immunosorbent assays. Expression of IL-1β, TGF-β1, LDLr, SREBP-2, SCAP, and apoB100 was higher in samples from patients with non-minimal change necrotic syndrome (NMCNS) compared to both controls and patients with minimal change necrotic syndrome. Deposition of apoB100 was significantly correlated with expression of IL-1β, TGF-β1, LDLr, SREBP-2, and SCAP and with the glomerulosclerosis index, but not with plasma lipid levels. Expression of IL-1β and TGF-β1 was significantly correlated with expression of LDLr, SREBP-2, and SCAP. These findings suggest that inflammation leads to lipid accumulation in the kidney through disruption of the expression of proteins in the SCAP/SREBP-2/LDLr signaling pathway, which may underlie glomerulosclerosis and tubulointerstitial fibrosis in NMCNS.

Citing Articles

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Zheng Z, Chen G, Jing X, Liu L, Yang L Transl Pediatr. 2022; 10(12):3184-3193.

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P2X7R antagonist protects against renal injury in mice with adriamycin nephropathy.

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Inflammation Induces Lipid Deposition in Kidneys by Downregulating Renal PCSK9 in Mice with Adriamycin-Induced Nephropathy.

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CD36 Promotes Podocyte Apoptosis by Activating the Pyrin Domain-Containing-3 (NLRP3) Inflammasome in Primary Nephrotic Syndrome.

Yang X, Wu Y, Li Q, Zhang G, Wang M, Yang H Med Sci Monit. 2018; 24:6832-6839.

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References

Goldstein J, Brown M . The LDL receptor and the regulation of cellular cholesterol metabolism. J Cell Sci Suppl. 1985; 3:131-7. DOI: 10.1242/jcs.1985.supplement_3.13. View

Abrass C . Cellular lipid metabolism and the role of lipids in progressive renal disease. Am J Nephrol. 2004; 24(1):46-53. DOI: 10.1159/000075925. View

Ruan X, Varghese Z, Powis S, Moorhead J . Dysregulation of LDL receptor under the influence of inflammatory cytokines: a new pathway for foam cell formation. Kidney Int. 2001; 60(5):1716-25. DOI: 10.1046/j.1523-1755.2001.00025.x. View

Ruan X, Moorhead J, Tao J, Ma K, Wheeler D, Powis S . Mechanisms of dysregulation of low-density lipoprotein receptor expression in vascular smooth muscle cells by inflammatory cytokines. Arterioscler Thromb Vasc Biol. 2006; 26(5):1150-5. DOI: 10.1161/01.ATV.0000217957.93135.c2. View

Takemura T, Yoshioka K, AYA N, Murakami K, Matumoto A, Itakura H . Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases. Kidney Int. 1993; 43(4):918-27. DOI: 10.1038/ki.1993.129. View

Rodriguez-Iturbe B, Quiroz Y, Shahkarami A, Li Z, Vaziri N . Mycophenolate mofetil ameliorates nephropathy in the obese Zucker rat. Kidney Int. 2005; 68(3):1041-7. DOI: 10.1111/j.1523-1755.2005.00496.x. View

Lin C, Chien J . Increased interleukin-12 release from peripheral blood mononuclear cells in nephrotic phase of minimal change nephrotic syndrome. Acta Paediatr Taiwan. 2004; 45(2):77-80. View

Rodriguez-Iturbe B, Herrera-Acosta J, Johnson R . Interstitial inflammation, sodium retention, and the pathogenesis of nephrotic edema: a unifying hypothesis. Kidney Int. 2002; 62(4):1379-84. DOI: 10.1111/j.1523-1755.2002.kid561.x. View

Cunard R, Kelly C . T cells and minimal change disease. J Am Soc Nephrol. 2002; 13(5):1409-11. DOI: 10.1097/01.asn.0000016406.82019.b3. View

10.

Diamond J, Karnovsky M . Focal and segmental glomerulosclerosis: analogies to atherosclerosis. Kidney Int. 1988; 33(5):917-24. DOI: 10.1038/ki.1988.87. View

11.

Kopp J, Factor V, Mozes M, Nagy P, Sanderson N, Bottinger E . Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive renal disease. Lab Invest. 1996; 74(6):991-1003. View

12.

Qin J, Zhang Z, Liu J, Sun L, Ling Hu , Cooper M . Effects of the combination of an angiotensin II antagonist with an HMG-CoA reductase inhibitor in experimental diabetes. Kidney Int. 2003; 64(2):565-71. DOI: 10.1046/j.1523-1755.2003.00127.x. View

13.

Habashy D, Hodson E, Craig J . Interventions for steroid-resistant nephrotic syndrome: a systematic review. Pediatr Nephrol. 2003; 18(9):906-12. DOI: 10.1007/s00467-003-1207-0. View

14.

Brown M, Goldstein J . A receptor-mediated pathway for cholesterol homeostasis. Science. 1986; 232(4746):34-47. DOI: 10.1126/science.3513311. View

15.

Ohtani H, Matoba K, Saika Y, Tanaka R, Yamada Y, Bando K . [Glomerular apolipoprotein B deposition in glomerular diseases]. Nihon Jinzo Gakkai Shi. 1990; 32(11):1145-52. View

16.

Ruan X, Varghese Z, Moorhead J . Inflammation modifies lipid-mediated renal injury. Nephrol Dial Transplant. 2002; 18(1):27-32. DOI: 10.1093/ndt/18.1.27. View

17.

Lee H, Lee J, Koh H, KO K . Intraglomerular lipid deposition in routine biopsies. Clin Nephrol. 1991; 36(2):67-75. View

18.

Sato H, Suzuki S, Ueno M, Shimada H, Karasawa R, Nishi S . Localization of apolipoprotein(a) and B-100 in various renal diseases. Kidney Int. 1993; 43(2):430-5. DOI: 10.1038/ki.1993.63. View

19.

Franzen R, Pautz A, Brautigam L, Geisslinger G, Pfeilschifter J, Huwiler A . Interleukin-1beta induces chronic activation and de novo synthesis of neutral ceramidase in renal mesangial cells. J Biol Chem. 2001; 276(38):35382-9. DOI: 10.1074/jbc.M102153200. View

20.

Keane W, Kasiske B, ODonnell M, Kim Y . The role of altered lipid metabolism in the progression of renal disease: experimental evidence. Am J Kidney Dis. 1991; 17(5 Suppl 1):38-42. View