Effects of Low Density Lipoprotein on Type IV Collagen Production by Cultured Rat Mesangial Cells

Kim, Soon Bae; Kang, Sin Ae; Cho, Young Joo; Park, Su-Kil; Cheong, Hae Il; Lee, Jae Dam; Hong, Changgi D.; Park, Jung Sik

doi:10.1159/000187988

Cited by 21 publications

(9 citation statements)

References 16 publications

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“…Lipoproteins can also induce the release of cytokines, like TGF-β and PDGF [36, 38]and increase the expression of chemoattractants like m-CSF and MCP-1 by mesangium cells [39, 40, 41]. LDL has also been found to promote in vitro mRNA expression of collagen IV and fibronectin, major components of the extracellular matrix [41, 42]. Our studies indicate a synergistic effect of hyperlipidemia to glomerular injury of hyperglycemia, but do not define the specific pathways by which this occurs.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia and Hyperlipidemia Act Synergistically to Induce Renal Disease in LDL Receptor-Deficient BALB Mice

Spencer¹,

Mühlfeld

Segerer

et al. 2004

Am J Nephrol

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Diabetic nephropathy is the leading cause of end-stage renal disease in Western countries, but only a portion of diabetic patients develop diabetic nephropathy. Dyslipidemia represents an important aspect of the metabolic imbalance in diabetic patients. In this study, we addressed the impact of combined hyperlipidemia and hyperglycemia on renal pathology. Kidneys from wild-type (WT) or LDL receptor-deficient BALB/cBy mice (BALB.LDLR–/–) were examined at 22 weeks of age. Diabetes was induced by administration of streptozotocin and mice were randomly assigned to either standard chow or Western diet. Chow fed BALB.LDLR–/– mice did not demonstrate renal abnormalities, whereas BALB. LDLR–/– mice fed a Western diet showed occasional glomerular and tubulointerstitial foam cells. Diabetic WT mice had modestly increased glomerular cellularity and extracellular matrix. Hyperlipidemic and diabetic BALB.LDLR–/– mice exhibited an increase in glomerular cellularity and extracellular matrix, accumulation of glomerular and tubulointerstitial foam cells and mesangial lipid deposits. The tubular epithelium demonstrated pronounced lipid induced tubular degeneration with increased tubular epithelial cell turnover. Hyperlipidemia and hyperglycemia seem to act synergistically in inducing renal injury in the BALB.LDLR–/– mouse. This model of diabetic nephropathy is unique in its development of tubular lesions and may represent a good model for hyperlipidemia-exacerbated diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Hyperglycemia and Hyperlipidemia Act Synergistically to Induce Renal Disease in LDL Receptor-Deficient BALB Mice

Spencer¹,

Mühlfeld

Segerer

et al. 2004

Am J Nephrol

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“…However, some authors have postulated that hyperlipidaemia is an important factor in the evolution of glomerulosclerosis [41][42][43]. Thus, Kim et al [44] showed that low-density lipoproteins (LDL) do stimulate in a dose-dependent manner the expression of mRNAs for the a 1 IV collagen chain as well as TIMP-2 in cultured rat mesangial cells. No significant effect of LDL on MMP-2 gene expression was found.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats

et al. 1997

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The obese Zucker rat is an autosomal recessive model of obesity and hyperlipidaemia with many similarities to human non-insulin-dependent diabetes mellitus (NIDDM) [1][2][3]. These metabolic abnormalities precede the development of albuminuria and mesangial matrix expansion followed by segmental glomerulosclerosis [4,5]. Accumulation of matrix components within the mesangium has been demonstrated for collagen IV, fibronectin, laminin and proteoglycans [6][7][8].The turnover of extracellular matrix is dependent on a balance between its synthesis and degradation, and consequently enhanced matrix deposition may be either due to increased synthesis and/or reduced activity of proteinases responsible for the remodelling of the matrix components. Several lines of evidence suggest the involvement of metalloproteinases Diabetologia (1997Diabetologia ( ) 40: 1035Diabetologia ( -1043 Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats Summary The obese Zucker rat represents a model of obesity combined with insulin resistance and hyperlipidaemia, which over a period of several months develops spontaneous glomerulosclerosis. The present study addressed the question as to whether glomerular sclerosis was associated with alterations in the degradation of matrix components. In the early phase (up to 6 months) glomeruli from obese rats displayed increased total collagen content (+ 64 %) and decreased gelatinolytic activity (− 34 %) as compared to lean control animals. This decline in glomerular gelatinolytic activity was due to a reduction in gelatinase B [matrix metalloproteinase (MMP)-9]. Glomerular MMP-9 mRNA was reduced 4.6 ± 0.6-fold (n = 3; p < 0.05), MMP-9 protein was not detectable by Western blotting and MMP-9 activity was considerably suppressed in gelatin zymograms. MMP-2, in terms of mRNA expression and activity, was unchanged. Tissue inhibitor of metalloproteinases (TIMP)-1 mRNA expression, TIMP-1 protein (immunohistochemistry) and TIMP-1 activity (reverse zymography) were enhanced in glomeruli from obese rats, while TIMP-2 mRNA remained unchanged. Moreover, mRNA for the a 1 IV collagen chain was 2.1 ± 0.8-fold higher in glomeruli isolated from obese animals (n = 3; p < 0.05). These findings indicate that matrix expansion in glomeruli from obese Zucker rats is due to both enhanced synthesis of matrix components as well as reduced degradation by matrix metalloproteinases. Apparently the latter effect is based on a reduction in MMP-9 and up-regulation of its inhibitor TIMP-1. [Diabetologia (1997[Diabetologia ( ) 40: 1035[Diabetologia ( -1043 Keywords Glomerulosclerosis, matrix metalloproteinase, tissue inhibitor of metalloproteinases, obese Zucker rat.Received: 16 January 1997 and in final revised form: 28 April, 1997Corresponding author: Dr. L. Schaefer, Med. Univ-Poliklinik, Albert-Schweitzer-Str. 33, 48129 Muenster, Germany Abbreviations: MMP, Matrix metalloproteinase; TIMP-1, -2: tissue inhibitor of metalloproteinases-1, -2; TPA, 12-O...

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“…22 In vitro studies have demonstrated that oxidized LDL stimulates the synthesis of collagen by vascular SMCs 23,24 and the expression of type IV collagen by mesangial cells. 25 Thus, these data suggest mutual influences between lipid and collagen that may affect lipid transport mechanisms and deposition as well as collagen synthesis.…”

mentioning

confidence: 81%

Cholesterol-Induced Changes of Type VIII Collagen Expression and Distribution in Carotid Arteries of Rabbit

Plenz

Dorszewski²,

Völker³

et al. 1999

ATVB

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Abstract-Lipoproteins play a major role in cardiovascular disease and atherosclerosis. In the vascular wall, they strongly influence the organization of extracellular matrix. The present study set out to investigate the changes in the extracellular matrix of the vessel wall induced by atherogenic diet, focusing on type VIII collagen, a vascular collagen that has not previously been investigated in detail. The influence of cholesterol diet on the expression, distribution, and deposition of type VIII collagen was examined in carotid arteries of New Zealand White rabbits. Carotid arteries of rabbits receiving diet supplemented with 1% cholesterol for 6 weeks and those on the same regimen followed by normal chow for 1 day, 10 days, 5 weeks, and 12 weeks were studied and compared with controls not exposed to the cholesterol diet. Carotid arteries of normocholesterolemic rabbits contained type VIII collagen-expressing cells in all layers, with focal accumulations of expressing cells in the subendothelial areas, the outer medial zone, and the adventitia. In response to cholesterol diet, type VIII collagen synthesis was reduced in media and adventitia and the distribution patterns changed. Expressing cells were found predominantly in the endothelium, and type VIII collagen accumulated in the intimal space.Immunogold labeling for electron microscopy revealed that type VIII collagen in the intima is associated with microfibrils extending from the internal elastic lamina. Withdrawal of cholesterol resulted in reestablishment of the normal distribution pattern. Northern and Western blot analyses supported the immunoconfocal and in situ hybridization data, demonstrating decreased type VIII collagen expression in response to cholesterol diet and progressive recovery to normal levels with time after withdrawal of cholesterol.

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Effects of Low Density Lipoprotein on Type IV Collagen Production by Cultured Rat Mesangial Cells

Cited by 21 publications

References 16 publications

Hyperglycemia and Hyperlipidemia Act Synergistically to Induce Renal Disease in LDL Receptor-Deficient BALB Mice

Hyperglycemia and Hyperlipidemia Act Synergistically to Induce Renal Disease in LDL Receptor-Deficient BALB Mice

Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats

Cholesterol-Induced Changes of Type VIII Collagen Expression and Distribution in Carotid Arteries of Rabbit

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