Protective Effect of Three Xanthine Derivatives (Theophylline, Caffeine and Pentoxifylline) against the Cyclosporin A-lnduced Glomerular Contraction in Isolated Glomeruli and Cultured Mesangial Cells

Nephron ◽  
1997 ◽  
Vol 77 (4) ◽  
pp. 427-434 ◽  
Author(s):  
M. Potier ◽  
M. Aparici ◽  
J. Cambar
Keyword(s):  
Protective Effect ◽  
Cyclosporin A ◽  
Mesangial Cells ◽  
Isolated Glomeruli ◽  
Xanthine Derivatives

Protective effect of cyclosporin A on brain injury in rats with acute necrotic pancreatitis

Life Sciences ◽  
2010 ◽  
Vol 87 (1-2) ◽  
pp. 64-68 ◽  
Author(s):  
Nian-Song Qian ◽  
Xiao-Ping Xu ◽  
Yong Chen ◽  
Ke-Feng Dou ◽  
Ya-Yun Wang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Protective Effect ◽  
Cyclosporin A ◽  
Necrotic Pancreatitis

scholarly journals Prolyl Hydroxylase Domain Inhibitor Protects against Metabolic Disorders and Associated Kidney Disease in Obese Type 2 Diabetic Mice

2020 ◽  
Vol 31 (3) ◽  
pp. 560-577 ◽  
Author(s):  
Mai Sugahara ◽  
Shinji Tanaka ◽  
Tetsuhiro Tanaka ◽  
Hisako Saito ◽  
Yu Ishimoto ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Transcriptome Analysis ◽  
Metabolic Disorders ◽  
Mesangial Cells ◽  
Endothelial Damage ◽  
Prolyl Hydroxylase ◽  
Macrophage Infiltration ◽  
Isolated Glomeruli ◽  
Prolyl Hydroxylase Domain

BackgroundProlyl hydroxylase domain (PHD) inhibitors, which stimulate erythropoietin production through the activation of hypoxia-inducible factor (HIF), are novel therapeutic agents used for treating renal anemia. Several PHD inhibitors, including enarodustat, are currently undergoing phase 2 or phase 3 clinical trials. Because HIF regulates a broad spectrum of genes, PHD inhibitors are expected to have other effects in addition to erythropoiesis, such as protection against metabolic disorders. However, whether such beneficial effects would extend to metabolic disorder–related kidney disease is largely unknown.MethodsWe administered enarodustat or vehicle without enarodustat in feed to diabetic black and tan brachyury (BTBR) ob/ob mice from 4 to 22 weeks of age. To elucidate molecular changes induced by enarodustat, we performed transcriptome analysis of isolated glomeruli and in vitro experiments using murine mesangial cells.ResultsCompared with BTBR ob/ob mice that received only vehicle, BTBR ob/ob mice treated with enarodustat displayed lower body weight, reduced blood glucose levels with improved insulin sensitivity, lower total cholesterol levels, higher adiponectin levels, and less adipose tissue, as well as a tendency for lower macrophage infiltration. Enarodustat-treated mice also exhibited reduced albuminuria and amelioration of glomerular epithelial and endothelial damage. Transcriptome analysis of isolated glomeruli revealed reduced expression of C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) in enarodustat-treated mice compared with the vehicle-only group, accompanied by reduced glomerular macrophage infiltration. In vitro experiments demonstrated that both local HIF-1 activation and restoration of adiponectin by enarodustat contributed to CCL2/MCP-1 reduction in mesangial cells.ConclusionsThese results indicate that the PHD inhibitor enarodustat has potential renoprotective effects in addition to its potential to protect against metabolic disorders.

scholarly journals Suppression by cyclosporin A of interleukin 1β -induced expression of group II phospholipase A2 in rat renal mesangial cells

1997 ◽  
Vol 121 (4) ◽  
pp. 787-793 ◽  
Author(s):  
Gaby Walker ◽  
Dieter Kunz ◽  
Werner Pignat ◽  
Henk van den Bosch ◽  
Josef Pfeilschifter
Keyword(s):  
Phospholipase A2 ◽  
Cyclosporin A ◽  
Mesangial Cells ◽  
Interleukin 1Β ◽  
Induced Expression ◽  
Group Ii

scholarly journals Tissue culture of isolated glomeruli in experimental crescentic glomerulonephritis.

1978 ◽  
Vol 147 (1) ◽  
pp. 98-109 ◽  
Author(s):  
S R Holdsworth ◽  
N M Thomson ◽  
E F Glasgow ◽  
J P Dowling ◽  
R C Atkins
Keyword(s):  
Tissue Culture ◽  
Inflammatory Reaction ◽  
Crescentic Glomerulonephritis ◽  
Mesangial Cells ◽  
Fc Receptors ◽  
Substantial Proportion ◽  
Cell Populations ◽  
Phagocytic Capacity ◽  
Isolated Glomeruli ◽  
Large Numbers

As a means of studying mechanisms of response to injury in glomerulonephritis, glomeruli from normal sheep and rabbits and from sheep and rabbits with experimental crescentic glomerulonephritis have been isolated and grown in tissue culture. The cellular outgrowths from the normal and diseased glomeruli have been compared. The outgrowth of glomeruli from normal animals contained only two cell populations whose microscopic and ultrastructural appearances were of epithelial and mesangial cells. The same cells were also observed in the outgrowths of glomeruli from animals with crescenti nephritis but in addition a third population of cells was present in large numbers. These cells were identified as macrophages by their mobility, ultrastructure, phagocytic capacity, and presence of Fc receptors. Glomerular outgrowth from sheep with crescentic glomerulonephritis contained 170 +/- 20 (SEM) macrophages and outgrowths from rabbits with crescentic nephritis contained 64 +/- 6 (SEM) macrophages per glomerulus. We have previously observed large numbers of macrophages in the outgrowth of isolated glomeruli from humans with rapidly progressive crescentic glomerulonephritis. The predominance of the macrophage in cultures of glomeruli from both human and animal crescentic glomerulonephritis suggests that this is an important cell in the inflammatory reaction occurring in crescentic glomerulonephritis and may comprise a substantial proportion of the cells forming the crescent.

Spontaneous activation of the NF-κB signaling pathway in isolated normal glomeruli

2006 ◽  
Vol 291 (6) ◽  
pp. F1169-F1176 ◽  
Author(s):  
Kunihiro Hayakawa ◽  
Yiman Meng ◽  
Nobuhiko Hiramatsu ◽  
Ayumi Kasai ◽  
Jian Yao ◽  
...  
Keyword(s):  
Map Kinase ◽  
Map Kinases ◽  
Mesangial Cells ◽  
Ex Vivo ◽  
P38 Map Kinase ◽  
Paracrine Factors ◽  
Enhancer Element ◽  
Monocyte Chemoattractant Protein 1 ◽  
Isolated Glomeruli ◽  
Tnf Α

In this report, we describe that NF-κB is spontaneously activated in isolated, normal glomeruli. Ex vivo incubation of isolated rat glomeruli triggered expression of a NF-κB-dependent gene, monocyte chemoattractant protein-1 (MCP-1), in parallel with downregulation of IκBα and IκBβ proteins and activation of the p65 NF-κB subunit. The induction of MCP-1 was also observed in mesangial cells coincubated with isolated glomeruli or exposed to media conditioned by isolated glomeruli (GCM), which was abrogated by inhibition of NF-κB. The activation of NF-κB by glomerulus-derived factors was confirmed using reporter mesangial cells that produce secreted alkaline phosphatase (SEAP) under the control of the κB enhancer element. When the reporter cells were adoptively transferred into normal glomeruli, expression of SEAP mRNA and activity of SEAP were also upregulated in the explanted glomeruli. The molecular weight of factors responsible for activation of NF-κB was >50 kDa, and TNF-α was identified as one of glomerulus-derived activators. To examine upstream events involved, we focused on MAP kinases that are spontaneously activated in explanted glomeruli. Selective suppression of ERK or p38 MAP kinase significantly attenuated activation of NF-κB in mesangial cells triggered by coculture with isolated glomeruli. Interestingly, the suppressive effects by MAP kinase inhibitors were not observed in mesangial cells treated with GCM. These data suggested that NF-κB was spontaneously activated in explanted glomeruli via autocrine/paracrine factors including TNF-α and that the production of NF-κB activators by glomeruli was, at least in part, through MAP kinase pathways.

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