Plasma α2 macroglobulin is increased in nephrotic patients as a result of increased synthesis alone

Velden, Monique G.M. de Sain–van der; Rabelink, Ton J.; Reijngoud, Dirk-Jan; Gadellaa, Mireille M.; Voorbij, H. A. M.; Stellaard, Frans; Kaysen, George A.

doi:10.1046/j.1523-1755.1998.00018.x

Cited by 53 publications

(10 citation statements)

References 34 publications

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“…Expression of A2M mRNA is unique to the chicken oviduct. In humans, A2M is synthesized primarily in the liver [43,44] and as a major plasma protein, it makes up roughly 8-10% of the total protein in human blood [45,46]. However, in chickens, A2M (also known as ovomacroglobulin or ovostatin) is synthesized in the oviduct and found in egg whites [14,47,48].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of alpha 2 macroglobulin in response to dietylstilbestrol and in ovarian carcinomas in chickens

Lim

Jeong

Kim

et al. 2011

Reprod Biol Endocrinol

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BackgroundAlpha 2 macroglobulin (A2M; also known as ovostatin), a homotetrameric protein with four disulfide-linked subunits, has the unique feature of inactivating/inhibiting most known proteases including serine-, threonine-, cysteine-, aspartic- and metalloproteases. In chickens, A2M has been identified and characterized biochemically, but little is known of its functional role(s) in the oviduct, hormonal regulation of expression or its expression in ovarian carcinomas in chickens. Therefore, we investigated estrogen regulation of A2M gene expression during development of the chicken oviduct, and its expression in normal and cancerous ovaries from chickens.MethodsTo determine tissue-specific expression of A2M in chickens, we collected various organs from male and female chickens and performed RT-PCR analyses. To examine A2M gene expression in the oviduct of 1-week-old female chicks that received a subcutaneous implant of 15 mg DES in the abdominal region for 20 days, we performed RT-PCR, qPCR and in situ hybridization analyses using cDNAs from control- (n = 5) and DES-treated oviducts (n = 5), and then each segment of the oviduct from DES-treated chicks. To determine if A2M is a biomarker of ovarian cancer in hens, we collected cancerous (n = 10) ovaries from a total of 136 chickens which had completely stopped egg-laying and performed RT-PCR and in situ hybridization analyses.ResultsWe found that A2M is most abundant in the chicken oviduct, specifically luminal (LE) and glandular epithelia (GE), but it was not detected in any other tissues of either sex. We then determined that DES (dietylstilbestrol, a synthetic nonsteroidal estrogen) increased A2M mRNA only in LE and GE of the oviduct of chicks. Further, expression of A2M was most abundant in GE of endometrioid adenocarcinoma of cancerous, but not normal ovaries of hens.ConclusionsCollectively, results of the present study indicate that A2M is novel estrogen-stimulated gene expressed in LE and GE of the chicken oviduct and may be used for monitoring effects of therapies for ovarian cancer in laying hens.

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Section: Discussionmentioning

confidence: 99%

Differential expression of alpha 2 macroglobulin in response to dietylstilbestrol and in ovarian carcinomas in chickens

Lim

Jeong

Kim

et al. 2011

Reprod Biol Endocrinol

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“…Our immunohistochemical findings showed that both groups of AD-treated rats had higher immunostaining for angiotensin II, endothelin and TGF-β in the tubular cells from the renal cortex. Several lines of evidence support a role for angiotensin II and endothelin in the progression of renal disease [11, 19, 45, 46, 47]. The presence of angiotensin II in the cytoplasm of tubular cells from these animals suggests an increase in ultrafiltration and reabsorption of this polypeptide, which has been reported to stimulate TGF-β production [45].…”

Section: Discussionmentioning

confidence: 99%

Heparin Treatment Reduces Glomerular Injury in Rats with Adriamycin-Induced Nephropathy but Does Not Modify Tubulointerstitial Damage or the Renal Production of Transforming Growth Factor-Beta

Baroni¹,

Costa

Silva³

et al. 2000

Nephron

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In this study we investigated the effect of heparin on renal injury and renal transforming growth factor-β (TGF-β) production in adriamycin (AD)-injected rats. Thirty-nine female Wistar rats were injected with AD (3.5 mg/kg body weight, i.v.) and 27 with 0.15 M NaCl solution (group C). Fifteen days later we started to inject heparin, 500 U/day, s.c., in 20 of the AD-injected animals (AD-H group). Three months after beginning treatment, urine samples were collected to quantify albumin, creatinine and TGF-β. The rats were killed and the kidneys removed for histological, immunohistochemical, ELISA and RNA studies. All AD-injected animals showed structural renal changes (p < 0.05). However, the glomerular alterations were less intense in rats from group AD-H (p < 0.05). The percentage of glomerulosclerosis was 0.11 ± 0.08 in group C, 14.7 ± 12.8 in group AD (treated only with AD) and 3.42 ± 2.3 in group AD-H. Renal cortex immunostaining for TGF-β and mRNA content of this polypeptide was higher in both groups of animals injected with AD compared to controls (p < 0.05). These animals also presented a higher rate of urinary TGF-β excretion (p < 0.05), which was 202 ± 11 in group C, 1,103 ± 580 in group AD and 1,564 ± 328 pg/mg Ucreat in group AD-H. However, TGF-β activity in the glomerular-conditioned media from the rats of group AD was higher than in the glomerular-conditioned media from the rats of group AD-H. In conclusion, treatment with heparin reduces glomerular damage in rats with AD-induced nephropathy but does not modify tubulointerstitial lesions or the renal production of TGF-β.

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“…However, data on the effect of peritoneal dialysis on serum CETP are lacking. Hepatic expression and serum concentration of CETP are elevated in patients with heavy proteinuria [36,37]. Given the significant losses of proteins with peritoneal dialysis procedure, we speculate that serum CETP may be elevated in patients undergoing peritoneal dialysis.…”

Section: Hdl Metabolism and Function In Ckdmentioning

confidence: 99%

Lipid Disorders and Their Relevance to Outcomes in Chronic Kidney Disease

2011

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Cardiovascular disease is the major cause of death in patients with chronic kidney disease (CKD). Cardiovascular disease and many other complications of CKD are mediated by oxidative stress, inflammation, and dyslipidemia. This review provides a concise overview of the nature and mechanisms of CKD-induced lipid disorders and their adverse consequences. Lipid abnormalities in end-stage renal disease are characterized by: (a) reduced serum apoA-1 and high-density lipoprotein (HDL) concentrations, impaired HDL maturation and defective HDL antioxidant, anti-inflammatory and reverse cholesterol transport properties; (b) impaired clearance of very low-density lipoprotein and chylomicrons by the muscle and adipose tissue and of their remnants by the liver leading to hypertriglyceridemia, accumulation of intermediate-density lipoprotein and chylomicron remnants, and (c) oxidative modification of LDL and lipoprotein remnants favored by their structural abnormalities, oxidative stress, and impaired HDL antioxidant activity. Together these abnormalities result in: (a) uptake of oxidized LDL and remnant particles by macrophages and resident cells in the artery wall which along with impaired HDL-mediated reverse cholesterol transport causes foam cell formation and atherosclerosis, (b) production of inflammatory mediators and reactive oxygen species by leukocytes and macrophages in response to stimulation by oxidized LDL and phospholipids leading to intensification of oxidative stress and inflammation, (c) dissemination of oxidative stress by circulating oxidized lipids and lipoproteins via lipid peroxidation chain reaction, (d) heightened injurious effects of oxidative stress and inflammation due to diminished antioxidant, anti-inflammatory and antithrombotic activities of HDL, and finally (e) impaired ability of very low-density lipoprotein and chylomicron to deliver lipid fuel to muscle and adipose tissue contributing to muscle weakness and cachexia which commonly occur in end-stage renal disease patients.

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Plasma α2 macroglobulin is increased in nephrotic patients as a result of increased synthesis alone

Abstract: Increased plasma alpha 2M concentration in nephrotic patients is therefore a result of increased synthesis alone.

Cited by 53 publications

References 34 publications

Differential expression of alpha 2 macroglobulin in response to dietylstilbestrol and in ovarian carcinomas in chickens

Differential expression of alpha 2 macroglobulin in response to dietylstilbestrol and in ovarian carcinomas in chickens

Heparin Treatment Reduces Glomerular Injury in Rats with Adriamycin-Induced Nephropathy but Does Not Modify Tubulointerstitial Damage or the Renal Production of Transforming Growth Factor-Beta

Lipid Disorders and Their Relevance to Outcomes in Chronic Kidney Disease

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