scholarly journals Intraglomerular Monocyte/Macrophage Infiltration and Macrophage–Myofibroblast Transition during Diabetic Nephropathy Is Regulated by the A2B Adenosine Receptor

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1051 ◽  
Author(s):  
Ángelo Torres ◽  
Katherin Muñoz ◽  
Yessica Nahuelpán ◽  
Angelo-Paolo R. Saez ◽  
Pablo Mendoza ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Cell Migration ◽  
Adenosine Receptor ◽  
Clinical Signs ◽  
Diabetic Rats ◽  
Macrophage Infiltration ◽  
A2b Adenosine Receptor ◽  
In Vivo Administration

Diabetic nephropathy (DN) is considered the main cause of kidney disease in which myofibroblasts lead to renal fibrosis. Macrophages were recently identified as the major source of myofibroblasts in a process known as macrophage–myofibroblast transition (MMT). Adenosine levels increase during DN and in vivo administration of MRS1754, an antagonist of the A2B adenosine receptor (A2BAR), attenuated glomerular fibrosis (glomerulosclerosis). We aimed to investigate the association between A2BAR and MMT in glomerulosclerosis during DN. Kidneys/glomeruli of non-diabetic, diabetic, and MRS1754-treated diabetic (DM+MRS1754) rats were processed for histopathologic, transcriptomic, flow cytometry, and cellular in vitro analyses. Macrophages were used for in vitro cell migration/transmigration assays and MMT studies. In vivo MRS1754 treatment attenuated the clinical and histopathological signs of glomerulosclerosis in DN rats. Transcriptomic analysis demonstrated a decrease in chemokine-chemoattractants/cell-adhesion genes of monocytes/macrophages in DM+MRS1754 glomeruli. The number of intraglomerular infiltrated macrophages and MMT cells increased in diabetic rats. This was reverted by MRS1754 treatment. In vitro cell migration/transmigration decreased in macrophages treated with MRS1754. Human macrophages cultured with adenosine and/or TGF-β induced MMT, a process which was reduced by MRS1754. We concluded that pharmacologic blockade of A2BAR attenuated some clinical signs of renal dysfunction and glomerulosclerosis, and decreased intraglomerular macrophage infiltration and MMT in DN rats.

Sequoyitol ameliorates diabetic nephropathy in diabetic rats induced with a high-fat diet and a low dose of streptozotocin

2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Low Dose ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
High Fat

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.

scholarly journals Effect of Tongxinluo on Nephrin Expression via Inhibition of Notch1/Snail Pathway in Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Fangqiang Cui ◽  
Dawei Zou ◽  
Yanbin Gao ◽  
Na Zhang ◽  
Jinyang Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanism ◽  
High Glucose ◽  
Diabetic Rats ◽  
In Vitro Studies ◽  
Podocyte Injury ◽  
Snail Expression ◽  
Renal Structure

Podocyte injury is an important mechanism of diabetic nephropathy (DN). Accumulating evidence suggests that nephrin expression is decreased in podocyte in DN. Moreover, it has been demonstrated that tongxinluo (TXL) can ameliorate renal structure disruption and dysfunction in DN. However, the effect of TXL on podocyte injury in DN and its molecular mechanism is unclear. In order to explore the effect of TXL on podocyte injury and its molecular mechanism in DN, our in vivo and in vitro studies were performed. Our results showed that TXL increased nephrin expression in diabetic rats and in high glucose cultured podocyte. Meanwhile, TXL decreased ICN1 (the intracellular domain of notch), HES1, and snail expression in podocyte in vivo and in vitro. More importantly, we found that TXL protected podocyte from injury in DN. The results demonstrated that TXL inhibited the activation of notch1/snail pathway and increased nephrin expression, which may be a mechanism of protecting effect on podocyte injury in DN.

scholarly journals Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 950 ◽  
Author(s):  
Shu Horikoshi ◽  
Noboru Fukuda ◽  
Akiko Tsunemi ◽  
Makiyo Okamura ◽  
Masari Otsuki ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Target Genes ◽  
Mesangial Cells ◽  
Diabetic Rats ◽  
Histological Evaluation ◽  
Renal Diseases ◽  
Podocyte Injury ◽  
Tgf Β1

TGF-β1 has been known to induce diabetic nephropathy with renal fibrosis and glomerulosclerosis. DNA-recognized peptide compound pyrrole-imidazole (PI) polyamides as novel biomedicines can strongly bind promoter lesions of target genes to inhibit its transcription. We have developed PI polyamide targeting TGF-β1 for progressive renal diseases. In the present study, we evaluated the contribution of TGF-β1 in the pathogenesis of diabetic nephropathy, and examined the effects of PI polyamide targeting TGF-β1 on the progression of diabetic nephropathy in rats. For in vitro experiments, rat renal mesangial cells were incubated with a high (25 mM) glucose concentration. Diabetic nephropathy was established in vivo in eight-week-old Wistar rats by intravenously administering 60 mg/kg streptozotocin (STZ). We examined the effects of PI polyamide targeting TGF-β1 on phenotype and the growth of mesangial cells, in vitro, and the pathogenesis of diabetic nephropathy in vivo. High glucose significantly increased expression of TGF-β1 mRNA, changed the phenotype to synthetic, and increased growth of mesangial cells. STZ diabetic rats showed increases in urinary excretions of protein and albumin, glomerular and interstitial degenerations, and podocyte injury. Treatment with PI polyamide targeting TGF-β1 twice weekly for three months improved the glomerular and interstitial degenerations by histological evaluation. Treatment with PI polyamide improved podocyte injury by electron microscopy evaluation. These findings suggest that TGF-β1 may be a pivotal factor in the progression of diabetic nephropathy, and PI polyamide targeting TGF-β1 as a practical medicine may improve nephropathy.

Anticoagulant Properties of Three Mucopolysaccharides Used in Rheumatology

1983 ◽  
Vol 50 (03) ◽  
pp. 652-655 ◽  
Author(s):  
F Bauer ◽  
P Schulz ◽  
G Reber ◽  
C A Bouvier
Keyword(s):  
Factor Xa ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Thrombin Time ◽  
Coagulation Tests ◽  
Amplification System ◽  
Relative Potencies ◽  
In Vivo Administration

SummaryThree mucopolysaccharides (MPS) used in the treatment of degenerative joint disease were compared to heparin to establish their relative potencies on 3 coagulation tests, the aPTT, the antifactor X a activity and the dilute thrombin time. One of the compounds, Arteparon®, was one fourth as potent as heparin on the aPTT, but had little or no influence on the 2 other tests. Further in vitro studies suggested that Arteparon® acted at a higher level than factor Xa generation in the intrinsic amplification system and that its effect was independent of antithrombin III. In vivo administration of Arteparon® confirmed its anticoagulant properties, which raises the question of the clinical use of this MPS.

Short-Chain Fatty Acids Prevent Diabetic Nephropathy In Vivo and In Vitro

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 92-OR ◽  
Author(s):  
WEI HUANG ◽  
YONG XU ◽  
YOUHUA XU ◽  
LUPING ZHOU ◽  
CHENLIN GAO
Keyword(s):  
Fatty Acids ◽  
Diabetic Nephropathy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

scholarly journals Amelioration of lipid peroxidation in vivo and in vitro by Satureja khozestanica essential oil in alloxan-induced diabetic rats

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Hassan Ahmadvand ◽  
Majid Tavafi ◽  
Ali Khosrowbeygi ◽  
Gholamreza Shahsavari ◽  
Maryam Hormozi ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Essential Oil ◽  
Diabetic Rats

scholarly journals FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo

2021 ◽  
Vol 22 (14) ◽  
pp. 7666
Author(s):  
Sara C. Credendino ◽  
Marta De Menna ◽  
Irene Cantone ◽  
Carmen Moccia ◽  
Matteo Esposito ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
Thyroid Cells ◽  
Transcriptional Alterations ◽  
Cancer Phenotypes

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

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