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G Ding

Publications and source records attributed to G Ding.

52 records · Page 3Linked to original sources
PubMed1993

Cholesterol, macrophages, and gene expression of TGF-beta 1 and fibronectin during nephrosis.

Hypercholesterolemia aggravates experimental progressive glomerular injury. Evidence suggests the infiltrating glomerular macrophage (M phi) is a potential effector mechanism for the noxious effects of hypercholesterolemia. Because transforming growth factor (TGF)-beta 1 is secreted by activated M phi s and also stimulates fibronectin production by glomerular cells, we evaluated the kinetics of gene expression for these moieties in glomeruli isolated from nephrotic rats at 3, 7, 11, and 42 days after the delivery of puromycin aminonucleoside (PA). We also assessed whether cholesterol feeding, which raises the glomerular M phi number, alters the glomerular mRNA levels for TGF-beta 1 and fibronectin. Glomerular mRNA levels for TGF-beta 1 and fibronectin in nephrotic rats exhibited a biphasic temporal pattern, decreasing significantly below control at 3 and 7 days after PA but increasing significantly at 11 and 42 days after PA. The upregulated gene expression for TGF-beta 1 and fibronectin at 11 days after PA temporally corresponded to the phase of mesangial M phi infiltration in this model. Cholesterol feeding to both normal and nephrotic rats significantly increased glomerular TGF-beta 1 and fibronectin mRNA levels at 11 days after PA. Immunohistochemical labeling for M phi s and intracellular TGF-beta 1 demonstrated both mesangial and cortical interstitial localization with the TGF-beta1-positive cells possessing M phi nuclear morphology. These findings identify a novel interaction between hypercholesterolemia, augmented glomerular M phi accumulation, and upregulated glomerular TGF-beta 1 and fibronectin gene expression. These perturbations within the acutely injured glomerulus constitute an early pathobiological determinant for the later development of mesangial matrix expansion and glomerulosclerosis.

Albuminuria↗
PubMed1992

Serum factor(s) induced by restraint stress in mice and rats suppresses lymphocyte proliferation.

LACA mice were individually restrained in a specially made cylindrical cage for 10-20 h at room temperature (20 degrees C). Serum obtained from stressed mice was found to suppress normal mouse lymphocyte proliferation induced by concanavalin A, suggesting the presence of a suppressive factor(s) in the stressed serum. Adrenalectomy or injections of naltrexone (1, 10, or 20 mg/kg, ip), just prior to and in the middle of the stress period, did not affect the suppressive activity of serum from mice. However, the suppressive activity was totally abolished by general anesthesia with urethane (1.5 g/kg, ip). These results suggest that adrenal hormones and opiate receptors are not involved in the generation of the suppressive factor(s) and that the central nervous system plays a very important role in this process. SD rats were restrained in a supine position for 20 h at room temperature (20 degrees C) and serum from stressed rats was also found to be able to suppress normal mouse lymphocyte proliferation. A further analysis of "stressed serum" indicated that the suppressive factor(s) was heat stable (56 degrees C, 30 min) and acid stable (pH 3.8), but sensitive to 100 degrees C (3 min), an organic solvent (greater than 60% methanol), and proteinases (trypsin and chymotrypsin). From the measurement of gel filtration (HPLC), the molecular weights of the suppressive factor(s) were 155 and 370 kDa. Taken together, these results indicate that the suppressive factor(s) is a protein with a large molecular weight.

Adrenalectomy↗
PubMed1992

Progressive albuminuria and glomerulosclerosis in a rat model of chronic renal allograft rejection.

A significant proportion of renal allografts fail within several months or years after transplantation, primarily because of chronic rejection. The etiology and pathophysiology of this condition remain unclear. We studied the renal function, morphology, and immunohistology, in parallel, among F344-to-Lewis allografts (n = 23) and isografts (n = 13) over the course of 24 weeks. Only an initial 10-day course of CsA (5 mg/kg/day) was given to both groups to prevent acute rejection. Hypertension did not develop, although awake systolic blood pressure was significantly higher in allografts at the end of the study. Significant differences in urine albumin excretion (UalbV) between isografts and allografts were evident as early as 4 weeks after engraftment but rose dramatically by 20 weeks (3.3 +/- 0.7 vs. 21.2 +/- 3.7 mg/day, respectively, P < .001). This pattern continued until the conclusion of the study (5.0 +/- 1.1 vs. 53.5 +/- 7.6 mg/day, P < .001). Serum creatinine values were only significantly elevated in allografts at 16 weeks, which temporally corresponded to the dramatic increase in UalbV. However, renal blood flow and glomerular filtration rate, measured by paraaminohippurate and inulin clearances, respectively, were significantly lower in allografted organs, at 24 weeks. The frequency of glomerulosclerosis lesions was significantly increased in allografted kidneys at 24 weeks and correlated with UalbV values. Glomerular localization of mononuclear leukocyte subsets were equivalent between allografts and isografts; however, the numbers of interstitial macrophages, CD8+, and pan-T-cells were all significantly greater in allografts at 24 weeks. The infiltration of significantly greater numbers of macrophages and lymphocytes into the tubulointerstitium of the allograft group suggests a mononuclear leukocyte effector cell mediation of the progressive glomerular abnormalities in this model of chronic renal allograft rejection in the rat.

Albuminuria↗
PubMed1992

Effect of cytochalasin D on the actin cytoskeleton of the toad bladder epithelial cell.

Cytochalasins are widely used to determine the role of actin in cellular processes. Their actions include capping of the barbed end of actin filaments as well as dimer formation, nucleation, and polymerization. We determined the effect of cytochalasin D (CD) on F-actin in the toad urinary bladder, an epithelium in which vasopressin depolymerizes F-actin. At a low concentration (0.25 microM), CD depolymerized F-actin in the unstimulated cell; at higher concentrations, there was a progressive reduction of depolymerization until actual polymerization was seen. Vasopressin plus CD produced no greater depolymerization than vasopressin alone, suggesting that CD and vasopressin act to a large extent on the same pool of F-actin. CD plus vasopressin also enhanced the fusion rate of aggrephores compared with vasopressin alone, indicating that intact actin filaments retard aggrephore fusion. Despite the increase in aggrephore fusion, water flow was not enhanced by CD, confirming previous reports that intact actin filaments are required for water channel emergence or stabilization in the apical membrane. Vasopressin plus 1 microM CD produced a striking increase in microvillar length, direct evidence of the polymerizing action of CD in the cell.

Actins↗
PubMed1992

Macrophages mediate adverse effects of cholesterol feeding in experimental nephrosis.

We tested whether the deleterious effects of hypercholesterolemia, in a progressive glomerular disease model, may be mediated by infiltrating renal macrophages. A single sublethal dose of whole body X-irradiation (XI) delivered to rats with acute puromycin aminonucleoside (PA) nephrosis fed a high-cholesterol (HC) diet resulted in significantly greater inulin and p-aminohippurate (PAH) clearances at 11 days after PA without any alterations in circulating lipid levels, in contrast to nonirradiated HC-fed nephrotic controls. This functional protection was associated with significant declines in both glomerular and cortical interstitial macrophage number. Over the course of this 16-wk model, HC-fed PA rats had significantly less albuminuria as well as significantly fewer glomerulosclerosis (GS) lesions and less mesangial matrix expansion at the end of the study despite an equivalent degree of sustained hypercholesterolemia. This data suggests that reducing the infiltrating glomerular and cortical interstitial macrophage burden with XI during acute PA nephrosis, unaccompanied by any hypolipidemic effect, produces not only early salutary effects on renal function but also a significant amelioration of the progressive glomerulopathic features of this model. This is consistent with the hypothesis that the infiltrating renal macrophage, in large part, directly mediates the adverse effects of hypercholesterolemia in this model.

Acute Disease↗
PubMed1992

Effects of endogenous and exogenous calcitonin on inflammation-mediated osteopenia in the rat.

Inflammation-mediated osteopenia (IMO) in the rat is characterized by loss of bone mass within 3 weeks after induction of nonspecific inflammation (s.c. talcum injections) in growing rats. Histologically, this shows as marked inhibition of osteoblasts 3 days after the initiation of IMO. The role of calcitonin (CT) was investigated in the present study. A reversible increase of serum CT levels was found after intraperitoneal calcium challenge in rats on day 4 after induction of IMO, which was thought to be a result from calcium efflux from bone. No difference in stimulated serum CT levels between the rats with and without IMO was seen on any other day during 4 weeks after initiation of IMO. Bone loss after IMO was more pronounced in normocalcemic and euthyroid rats with deficiency of endogenous CT (thyroidectomy with parathyroid gland reimplanted) (-12.9%) compared with sham operated controls with IMO (-3.25%). Daily subcutaneous injections of 100 mIU salmon CT in rats with and without IMO did not prevent the development of bone loss. This might have been due to the growing state of rats of this age group. Our results support the hypothesis that endogenous CT physiologically has a bone protective role. They furthermore are consistent with the view that endogenous CT itself is not pathogenetically involved in the development of osteoporosis.

Animals↗
PubMed1992

Pharmacokinetics of [6]-gingerol after intravenous administration in rats with acute renal or hepatic failure.

The pharmacokinetics of [6]-gingerol were investigated in rats with acute renal failure induced by bilateral nephrectomy, or those with acute hepatic failure induced by a single oral administration of carbon tetrachloride (CCl4), to clarify the contribution of the kidney and liver to the elimination process of [6]-gingerol. After bolus intravenous administration, a plasma concentration-time curve of [6]-gingerol was illustrated by a two-compartment open model. There was no significant difference in either the plasma concentration-time curve or any pharmacokinetic parameters between the control and nephrectomized rats. It is suggested, therefore, that renal excretion does not contribute at all to the disappearance of [6]-gingerol from plasma in rats. In contrast, hepatic intoxication with CCl4 elevated the plasma concentration of [6]-gingerol at the terminal phase. Its elimination half-life increased significantly, from 8.5 to 11.0 min, in CCl4-intoxicated rats. The extent of [6]-gingerol bound to serum protein was more than 90% and was affected very slightly by the CCl4-intoxication. These aspects indicate that [6]-gingerol is eliminated partly by the liver.

Acute Disease↗
PubMed1992

Glomerular macrophages and the mesangial proliferative response in the experimental nephrotic syndrome.

Mesangial cell proliferation, which is a harbinger of glomerulosclerosis, occurs in both immune and nonimmune glomerulopathies. The proximity of infiltrating glomerular macrophages to the contractile mesangial cells during acute puromycin aminonucleoside (PA) nephrosis suggests the possibility of a paracrine effect on mesangial cell growth. To test this, three maneuvers to either raise or lower the glomerular macrophage number during acute PA nephrosis (2 weeks after PA) were employed: 1) an essential fatty acid-deficient (EFAD) diet; 2) a cholesterol-supplemented diet (CSD); and 3) a single dose (600 rad) whole-body X-irradiation (XI) given to CSD-fed PA rats. Both the glomerular macrophage number and proliferation within the mesangium were evaluated immunohistochemically with ED-1, a mouse monoclonal anti-rat macrophage label, and 19A2, a mouse monoclonal anti-proliferating cell nuclear antigen (PCNA)/cyclin antibody, respectively. Immunohistochemical detection of 5'-bromo-2'-deoxyuridine (BrdU) incorporation confirmed that proliferation was occurring within the mesangial zones. The EFAD diet significantly reduced both the glomerular macrophage and PCNA/cyclin-positive cell number at 2 weeks after PA with a positive correlation (r = 0.89, P < 0.05). The CSD maneuver significantly increased both the glomerular macrophage and PCNA/cyclin cell number with a strong degree of correlation (r = 0.95, P < 0.01). X-irradiation administered to CSD-fed PA rats significantly lowered both the glomerular macrophage and PCNA/cyclin-positive cell number at 2 weeks. In all groups, the glomerular tufts did not express muscle actin using HHF 35, a specific immunolabel, suggesting that the proliferation in this model is not related to direct mesangial cell injury. This study shows that maneuvers that modulate the glomerular macrophage number are also associated with corresponding changes in the number of proliferating cells within the mesangium, suggesting a paracrine growth stimulation by the infiltrating macrophage during acute PA nephrosis. The infiltrating glomerular macrophage may be an effector mechanism for the propagation of initial glomerular injury to glomerulosclerosis by augmenting mesangial cell proliferation early in the course of this nonimmune progressive glomerulopathy.

Animals↗
PubMed1991

[Effects of Epimedium sagittatum Maxim. Polysaccharides on DNA synthesis of bone marrow cells of "yang deficiency" animal model caused by hydroxyurea].

A study was made on the effects of Epimedium sagittatum polysaccharides on DNA synthesis of bone marrow cells of "yang deficiency" animal model caused by hydroxyurea with methods of cell culture in vitro and determination of 3H-TdR incorporating DNA of bone marrow cells. The results showed that after the treatment with 100 micrograms of Epimedium sagittatum polysaccharides, the cell multiplication rate was increased by 72% and DNA synthesis rate increased by 68%, in 1 x 10(6) cells.

Animals↗
PubMed1990

[Experimental study of thyroid hormone and bone metabolism in the rat].

Thyroid hormones (T3, T4) stimulate bone turnover. Calcitonin is a potent inhibitor of osteoporostic bone resorption. In patients with thyrotoxicosis, bone mineral content is reduced. We investigated the influence of calcitonin deficiency in thyroidectomized parathyroid-autotransplanted rats with L-thyroxine (T4) supplementation. Thyroidectomy resulted in a reduction of bone volume, bone calcium content and in a decrease in trabecular bone volume. T4-supplementation corrected this loss of bone calcium content but not trabecular bone volume. In thyroidectomized parathyroid-autotransplanted rats matched for T3-levels to intact controls, there was still a reduction in both bone calcium content and trabecular bone volume. We assume this decrease in bone mass in thyroidectomized parathyroid-autotransplanted animals to be caused by the lack of calcitonin.

Animals↗
PubMed1988

Role of vesicular transport in ADH-stimulated aggregate delivery.

It has been assumed from studies in toad bladder that antidiuretic hormone (ADH)-stimulated particle delivery to the luminal membrane is mediated by particle-carrying tubular structures (aggrephores). We report studies in frog and toad urinary bladder showing that vesicles, rather than aggrephores, appear to play the major role in particle delivery in the frog and that vesicle and aggrephore delivery proceed in parallel in the toad. Our principal evidence for this view is that in the frog, transmission electron microscopy shows virtually no fused aggrephores. Supporting evidence includes the following. 1) Freeze-fracture studies show that the diameters of fusion events delivering particles can be quite small, indicating that they are formed by fused vesicles rather than fused aggrephores. 2) A significant population of small fusion events is also seen in the toad, along with larger fusion events related to both aggrephores and large vesicles. 3) Surface aggregate areas in both species are small, consistent with vesicular delivery. 4) Freeze-fracture replicas indicate delivery from shallow pits. We propose a system of transport of particles in which aggrephores act largely as intermediate storage organelles in the frog and as storage and fusion organelles in the toad.

Animals↗
PubMed1985

Evidence for cycling of aggregate-containing tubules in toad urinary bladder.

Antidiuretic hormone (ADH) promotes the fusion of cytoplasmic tubular structures with the luminal membrane of receptor tissues such as toad urinary bladder. To determine whether fusion is a continuous cyclic process, bladders were stimulated with ADH with colloidal gold in the luminal bathing medium. After as little as 15 min of stimulation, gold-filled tubules were seen in the cytoplasm, evidence that cycling was indeed taking place. Serial sections confirmed that these tubules had no connection with the luminal membrane, and had returned to the cytoplasm. Cessation of ADH stimulation, followed by a second stimulation, greatly reduced the number of gold-filled cytoplasmic tubules, suggesting that many tubules were capable of refusion. Mean fusion event diameter underwent significant changes, enlarging at 15 min, and contracting at 60 min. Thus, ADH initiates a process of continuous cycling of cytoplasmic tubules between cytoplasm and luminal membrane.

Animals↗
PubMedDate not supplied

Alpha macroglobulins and the low-density-lipoprotein-related protein/alpha-2-macroglobulin receptor in experimental renal fibrosis.

In this study, we evaluated the location of non-specific proteinase inhibitors and their receptor in experimental glomerular and interstitial fibrosis. The alpha macroglobulins alpha-2-macroglobulin (alpha2M) and alpha-1-inhibitor 3 (alpha1I3) are proteinase inhibitors, including metalloproteinases and serine proteases. Using immunohistochemistry, we detected alpha1I3 in the glomerular mesangium in control rats. In acute and chronic fibrosis, the alpha1I3 protein expression was dramatically increased throughout the glomerulus and at sites of increased extracellular matrix deposition in the interstitium. The presence of alpha1I3 in normal and nephrotic kidneys was confirmed by Western blotting. Under chemically reducing conditions, we found that, in contrast to native alpha1I3, kidney-derived alpha1I3 has reacted upon by proteinases, thereby revealing a functional role for this macroglobulin under normal and pathological conditions. Double staining revealed that high amounts of glomerular alpha1I3 were present in sclerotic lesions. alpha2M was absent in glomeruli and interstitium from control rats, but present in small amounts in glomerular mesangial areas of acute nephrotic rats. alpha2M was also present in significant amounts in glomeruli from rats with chronic fibrosis. The receptor mediating the uptake of proteinase inhibitor-proteinase complexes, the low-density-lipoprotein-related protein/alpha-2-macroglobulin receptor, was found in the glomerular mesangium and tubulo-interstitium from control rats. Significant increments in receptor expression were found in glomeruli and interstitium of rats with chronic fibrosis, with a preferential localization in fibrotic areas. Interstitial staining for low-density-lipoprotein-related protein/alpha-2-macroglobulin receptor was attributed to fibroblasts, since double staining ruled out dendritic cells and macrophages. In conclusion, these studies demonstrate the intrarenal presence of plasma-derived proteinase inhibitors together with their receptors. These findings may point to a novel mechanism for renal fibrosis wherein matrix-degrading proteinases are inhibited, resulting in renal fibrosis.

Acute-Phase Proteins↗