scholarly journals Hypertriglyceridemia Is Associated with More Severe Histological Glomerulosclerosis in IgA Nephropathy

2021 ◽  
Vol 10 (18) ◽  
pp. 4236
Author(s):  
Won Jung Choi ◽  
Yu Ah Hong ◽  
Ji Won Min ◽  
Eun Sil Koh ◽  
Hyung Duk Kim ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Risk Factor ◽  
Iga Nephropathy ◽  
Mesangial Cell ◽  
Significant Risk ◽  
Density Lipoprotein ◽  
Significant Risk Factor ◽  
Mesangial Matrix ◽  
Mesangial Cell Proliferation ◽  
Matrix Expansion

IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males; higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio; and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.

scholarly journals Expression of Megsin mRNA, a Novel Mesangium-Predominant Gene, in the Renal Tissues of Various Glomerular Diseases

1999 ◽  
Vol 10 (12) ◽  
pp. 2606-2613
Author(s):  
DAISUKE SUZUKI ◽  
TOSHIO MIYATA ◽  
MASAOMI NANGAKU ◽  
HIDEO TAKANO ◽  
NOBORU SAOTOME ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Periodic Acid ◽  
Cell Number ◽  
Mesangial Matrix ◽  
Periodic Acid Schiff ◽  
Glomerular Diseases ◽  
Mesangial Cell Proliferation ◽  
Matrix Expansion

Abstract. Mesangial cells play an important role in maintaining a structure and function of the glomerulus and in the pathogenesis of glomerular diseases. Recently, we discovered a new mesangium-predominant gene termed “megsin.” Megsin is a novel protein that belongs to the serine protease inhibitor (serpin) superfamily. To elucidate the pathophysiologic role of megsin in the kidney, the expression and localization of megsin mRNA in renal tissues of patients with IgA nephropathy (IgA-N), diabetic nephropathy (DN), minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN), and normal human kidney (NHK) was evaluated by in situ hybridization using digoxigenin-labeled oligonucleotide. Individual cells positive for megsin mRNA were observed only in glomeruli in all renal tissues. Their localization coincided with those of mesangial cells. The percentage of positive cells for megsin mRNA in total glomerular cells was significantly greater in IgA-N than in MCNS, MN, and NHK. It was also significantly greater in DN than in MCNS and NHK. In IgA-N, the percentage of megsin mRNA-positive cells was greater in tissues from those with mesangial cell proliferation and slightly mesangial matrix expansion (periodic acid-Schiff-positive area in the total glomerulus area, <30%; cell number in mesangial matrix area, >30; assessed in cross-sections through their vascular poles) than in tissues from those with severe mesangial matrix expansion (periodic acid-Schiff-positive area in total glomerulus area, >30%; cell number in mesangial matrix area, <30). In conclusion, megsin mRNA was predominantly expressed in glomerular mesangial cells in all renal tissues. The expression of megsin mRNA was upregulated in IgA-N and DN, both of which are diseases accompanied with mesangial cell proliferation and/or mesangial matrix expansion. These data suggest a link of megsin expression to the pathogenesis of IgA-N and DN, two major causes of end-stage renal failure.

Effect of interleukin-6 receptor blockage on renal injury in apolipoprotein E-deficient mice

2009 ◽  
Vol 297 (3) ◽  
pp. F679-F684 ◽  
Author(s):  
Mari Tomiyama-Hanayama ◽  
Hiromi Rakugi ◽  
Masaharu Kohara ◽  
Toru Mima ◽  
Yasuo Adachi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Apolipoprotein E ◽  
Interleukin 6 ◽  
Renal Injury ◽  
Mesangial Cell ◽  
Organ Damage ◽  
Glomerular Injury ◽  
Mesangial Cell Proliferation ◽  
Matrix Expansion ◽  
Interleukin 6 Receptor

Hyperlipidemia has been demonstrated to be associated with renal disease, yet the mechanism of renal injury is still poorly understood. Inflammation that occurs with the hyperlipidemia has been considered to play an important role in development of glomerular injury. In the present study, we investigated the role of interleukin-6 (IL-6), a key inflammatory molecule, on renal injury in apolipoprotein E-deficient (ApoE−/−) mice with severe hypercholesterolemia. The 6-wk-old mice were fed a high-fat diet and administered weekly rat anti-IL-6 receptor monoclonal antibody (MR16-1), control rat IgG, or saline for a total of 4 wk. We examined histopathological changes in the kidney and urinary excretion of protein and albumin. Saline- and IgG-treated mice showed remarkable proteinuria at 10 wk of age, whereas MR16-1-treated mice exhibited significantly lower levels. Renal histopathology of saline- and IgG-treated mice revealed striking lipid deposits and foam cells in the glomerular tuft, juxtaglomerular area, and arteriolar wall along with range of mesangial cell proliferation and matrix expansion. Notably, the severity of lipid deposits and mesangial cell proliferation were significantly reduced in MR16-1-treated mice. Immunohistochemistry demonstrated that mesangial IL-6 expression was dramatically reduced in MR16-1-treated mice compared with IgG-treated mice. Blocking the IL-6 receptor prevented progression of proteinuria and renal lipid deposit, as well as the mesangial cell proliferation associated with severe hyperlipoproteinemia. These results clearly demonstrate that IL-6 plays an essential role in the pathogenesis of hyperlipidemia-induced glomerular injury in ApoE−/− mice and suggests the usefulness of anti-IL-6 receptor antibody in treatments for hyperlipidemia-induced organ damage.

IgA nephropathy and mesangial cell proliferation: shared global gene expression profiles

Nephrology ◽  
2002 ◽  
Vol 7 ◽  
pp. S106-S113
Author(s):  
Hideto SAKAI ◽  
Naohiro YANO ◽  
Kimberly J FADDEN-PAIVA ◽  
Masayuki ENDOH ◽  
Kiyoshi KUROKAWA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Iga Nephropathy ◽  
Mesangial Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Mesangial Cell Proliferation

scholarly journals Laminin α1 Regulates Age-Related Mesangial Cell Proliferation and Mesangial Matrix Accumulation through the TGF-β Pathway

2014 ◽  
Vol 184 (6) ◽  
pp. 1683-1694 ◽  
Author(s):  
Liang Ning ◽  
Hidetake Kurihara ◽  
Susana de Vega ◽  
Naoki Ichikawa-Tomikawa ◽  
Zhuo Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mesangial Cell ◽  
Mesangial Matrix ◽  
Age Related ◽  
Mesangial Cell Proliferation ◽  
Matrix Accumulation

IgA nephropathy and mesangial cell proliferation: shared global gene expression profiles

Nephrology ◽  
2002 ◽  
Vol 7 ◽  
pp. S106-S113 ◽  
Author(s):  
Hideto Sakai ◽  
Naohiro Yano ◽  
Kimberly J Fadden-Paiva ◽  
Masayuki Endoh ◽  
Kiyoshi Kurokawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Iga Nephropathy ◽  
Mesangial Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Mesangial Cell Proliferation

scholarly journals Simvastatin suppresses glomerular cell proliferation and macrophage infiltration in rats with mesangial proliferative nephritis.

1998 ◽  
Vol 9 (11) ◽  
pp. 2027-2039
Author(s):  
A Yoshimura ◽  
K Inui ◽  
T Nemoto ◽  
S Uda ◽  
Y Sugenoya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Coenzyme A ◽  
Mesangial Cell ◽  
Glomerular Cell ◽  
Simvastatin Treatment ◽  
Macrophage Recruitment ◽  
Mesangial Cell Proliferation ◽  
Matrix Expansion ◽  
Disease Induction ◽  
Coenzyme A Reductase

Inhibition of 3-hydro-3-methylglutaryl coenzyme A reductase inhibits the production of mevalonate and has been shown to suppress proliferation in many cell types. Therefore, 3-hydro-3-methylglutaryl coenzyme A reductase inhibitors may have a beneficial effect in glomerular disease, because glomerular cell proliferation is a central feature in the active glomerular injury. This study examines the effect of simvastatin on glomerular pathology in a rat mesangial proliferative glomerulonephritis (GN) induced by anti-thymocyte antibody (anti-Thy 1.1 GN). There was no difference in the degree of the antibody and complement-mediated initial injuries between simvastatin-treated and control GN rats. The most pronounced feature of simvastatin-treated GN was the suppression of the early glomerular cell proliferation. The proliferative activity was maximal at day 4 after disease induction (26.5+/-7.0 of proliferating cell nuclear antigen-positive cells/glomerulus); however, approximately 70% of proliferation was suppressed by simvastatin treatment. At day 4 after disease induction, simvastatin administration also decreased alpha-smooth muscle actin expression in the glomerulus, which is a marker for mesangial cell activation. Inhibition of monocyte/macrophage recruitment into glomeruli by simvastatin was also a prominent feature. There was a 30% decrease in the number of glomerular ED-1+ cells by simvastatin treatment at day 2 after disease induction. Furthermore, simvastatin remarkably suppressed subsequent mesangial matrix expansion and type IV collagen accumulation in glomeruli. We also found that the platelet-derived growth factor expression was reduced in simvastatin-treated nephritic rats, which might simply reflect the reduction in mesangial cell proliferation and mesangial cellularity. There was no significant difference in plasma cholesterol or triglyceride levels between simvastatin- and vehicle-treated nephritic rats at day 2 and day 4, which corresponded to the times when simvastatin treatment resulted in a reduction in mesangial cell proliferation. In conclusion, this is the first report to find that mesangial cell proliferation and matrix expansion have been blocked by simvastatin in vivo. The protective effect of simvastatin in the matrix expansion in anti-Thy1.1 GN was partly by inhibition of mesangial cell proliferation and monocyte/ macrophage recruitment into glomeruli, which were independent of a change in circulating lipids.

scholarly journals Heparin decreases mesangial matrix accumulation after selective antibody-induced mesangial cell injury.

1992 ◽  
Vol 3 (4) ◽  
pp. 921-929
Author(s):  
W W Tang ◽  
C B Wilson
Keyword(s):  
Cell Proliferation ◽  
Cell Injury ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Chronic Administration ◽  
Glomerular Mesangial Cells ◽  
Mesangial Matrix ◽  
Beneficial Effects ◽  
Mesangial Cell Proliferation ◽  
Matrix Accumulation

Anti-rat thymocyte antibody-induced injury of glomerular mesangial cells is characterized initially by lysis (1 h) and is followed by proliferation (beginning at 3 to 4 days), with resolution that can include a focal increase in mesangial matrix (by 28 days). Chronic administration (every 12 h) of heparin (anticoagulant or nonanticoagulant) resulted in a decrease in antibody-induced mesangial cell proliferation, which, in turn, was associated with a decrease in the size and number of areas of focal mesangial matrix increase. The effect could not be attributed to the effect of heparin on complement, to alterations in the small numbers of la-positive cells that characterize the lesion, or to binding of antibody to glomeruli. The beneficial effects of heparin in reducing mesangial cell proliferation, with a subsequent reduction in matrix increase, suggest that mesangial cell responses are a major element in the development of at least some forms of glomerulosclerosis. The possible mechanisms by which these effects of heparin may be achieved are discussed.

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