Browsing by Subject "Glomerulosclerosis"

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    Hypertension and Sex Differences in the Age-Related Renal Changes When Cyclooxygenase-2 Activity Is Reduced During Nephrogenesis
    (American Heart Association, 2008-12-22) Saez, Fara; Reverte, Virginia; Salazar, Francisco; Llinás, María Teresa; Salazar, F. Javier; Castells Mora, María Teresa; Fisiología
    Several studies have proposed that cyclooxygenase-2 (COX2) is involved in the regulation of nephrogenesis and that an impaired nephrogenesis may induce the development of hypertension. This study was designed to test the hypothesis that the decrease of COX2 activity leads to a reduction in nephron number, an increase in arterial pressure, and age-dependent renal alterations that are greater in male than in female rats. Arterial pressure was measured from the first to the 16th month of life in rats treated with vehicle or a COX2 inhibitor during the nephrogenic period. Stereological and histological evaluations and renal function studies were performed at different ages. Arterial pressure increased (14%; P<0.05) and nephron number decreased (17%; P<0.05) to similar levels in male and female COX2-treated rats. However, glomerular filtration rate (31%) and renal plasma flow (25%) decreased (P<0.05) in male but not in female COX2-treated rats. A greater (P<0.05) age-dependent elevation in glomerular hypertrophy was also found in male COX2-treated rats compared with their female littermates. Glomerulosclerosis and tubulointerstitial damage in renal cortex and medulla were also significantly enhanced in male but not in female aged COX2-treated rats. Our results demonstrate that the decrease in COX2 activity during renal development leads to a reduction in nephron number and to an elevation in arterial pressure that are similar in males and females. However, the consequent age-dependent deterioration of the renal structure and renal function is only significantly enhanced in male rats.
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    Less gelatinases is associated with apolipoprotein E accumulation in glomerulosclerosis rats
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Zhou, Tian-Biao; Qin, Yuan-Han; Lei, Feng-Ying; Su, Li-Na; Zhao, Jan-Jun; Huang, Wei-Fang
    Background: Gelatinases include matrix metalloproteinase-2 (MMP-2) and matrix metallo-proteinase-9 (MMP-9). The abnormal expressions of gelatinases are implicated in the pathogenesis of extracellular matrix (ECM) accumulation. Apolipo-protein E (apoE) is an important plasma protein in cholesterol homeostasis and plays a key role in the progression of glomerulosclerosis (GS). We conducted this investigation to explore whether gelatinases were associated with the apoE accumulation in the pathological process of GS. Methods: 40 Wistar rats were divided into two groups at random: sham operation group (SHO) and glomerulosclerosis model group (GS); n=20, respectively. The disease of GS was established by uninephrectomy and adriamycin (5 mg/kg) injection. At the end of 13 weeks, the 20 rats in each group were killed and the relevant samples were collected and measured. Results: Serum total protein (TP) and serum albumin (Alb) in GS group were reduced compared to those of the SHO group (P<0.01). Compared with the SHO group, values of 24-hour urine total protein (24UTP), 24-hour urine excretion for albumin (24Ualb), blood urea nitrogen (BUN), serum creatinine (Scr) and glomerulosclerosis index (GSI) in GS group were significantly increased (P<0.01). The protein of MMP-2 or MMP-9 in the glomerulus, and mRNA expression of MMP-2 or MMP-9 in renal tissue were reduced when compared with those in SHO (P<0.01). Protein expressions of apoE, collagen IV (Col-IV), fibronectin (FN), α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1) in the glomerulus and expression of apoE mRNA in renal tissue were significantly up-regulated in GS group when compared with those in the SHO group (P<0.01). Conclusions: Lower expression of gelatinases is associated with the increased expression of apoE in the glomerulus, and increases the accumulation of ECM and takes part in the pathological change of GS.
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    Mechanisms and consequences of hypertriglyceridemia and cellular lipid accumulation in chronic kidney disease and metabolic syndrome
    (F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Lee, Hyun Soon
    Hypertriglyceridemia and intracellular lipid overload are commonly present in both the chronic kidney disease (CKD) and metabolic syndrome. Hypertriglyceridemia in the metabolic syndrome arises mostly from increased lipoprotein synthesis, while that in the CKD is mainly caused by decreased catabolism. In metabolic syndrome, enhanced plasma levels of free fatty acids and triglyceride (TG) may lead to intracellular fatty acid accumulation in the kidney. However, the mechanisms by which intracellular lipid accumulation occurs in the dieased glomeruli have not been established. I provide evidence that binding/uptake of TG-rich very low-density lipoprotein by glomerular cells is increased in CKD, leading to increased endocytic accumulation of TG. I also provide evidence that cellular damage by fatty acid accumulation in the kidney is particularly severe in podocytes, leading to apoptosis and resulting in glomerulosclerosis. Collectively, these data bring new mechanistic insights into cellular lipid overload and lipotoxicity in CKD.
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    Structural changes in glomeruli and proteinuria in streptozotocin diabetic rats
    (Murcia : F. Hernández, 1989) Al-Awadi, Farida M.; Al-Adnani, M. S.
    In streptozotocin induced diabetes in rats, excretion of urinary protein fractions were studied in relation to structural changes in the renal glomeruli, using light and transmission electron microscopy. After six weeks of induced diabetes only 01 and B2 plasma globulins were significantly elevated. The amount of excreted proteins and degree of glomerular changes were not proportional. In the initial stages (1-2 weeks) glomerular structural changes were very mild and were accompanied by significantly elevated proteinuria. This progressed (4-8 weeks) to moderate to prominent structural changes with intermittent proteinuria except for the fractions 01 & B2 which were elevated throughout the duration of the experiment. The amount of proteinuria was not proportional to changes in the plasma protein levels. The following conclusions may be made: 1) The mild early glomerular abnormalities seem to be mainly due to acute metabolic disturbances. 2) An early indication of diabetic nephropathy is provided not only by albuminuria, but may also be an elevated excretion of betaglobulin fractions. 3) Decrease of albuminuria in the later stages of diabetes may be related to the deposition of albumin as a basement membrane - like material in the mesangium.
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    The possible role of colligin, HSP47, a collagen-binding protein, in the pathogenesis of human and experimental fibrotic diseases
    (Murcia : F. Hernández, 1999) Razzaque, M.S.; Taguchi, T.
    Colligin or heat shock protein 47 (HSP47) is a stress protein that resides in the endoplasmic reticulum and is thought to participate in intracellular processing, folding, assembly and secretion of procollagens. Irrespective of the tissue site and organ, induction of colliginlHSP47 expression is always noted during the process of fibrosis, particularly in and around the fibrotic lesions in both humans and experimental models. Its expression is highly tissue- and cell-specific, and restricted to mostly phenotypically altered collagenproducing cells. These observations suggest that upregulation of this collagen-specific chaperone-colliginl HSP47 may play an important role in the subsequent fibrotic process, possibly by regulating increased synthesis/assembly of collagens.