scholarly journals Dietary Chrysin Suppresses Formation of Actin Cytoskeleton and Focal Adhesion in AGE-Exposed Mesangial Cells and Diabetic Kidney: Role of Autophagy

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 127 ◽  
Author(s):  
Eun-Jung Lee ◽  
Min-Kyung Kang ◽  
Yun-Ho Kim ◽  
Dong Yeon Kim ◽  
Hyeongjoo Oh ◽  
...  
Keyword(s):  
Cell Motility ◽  
Focal Adhesion ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Smooth Muscle Actin ◽  
Actin Dynamics ◽  
Chronic Glomerulonephritis ◽  
Causative Role

Advanced glycation end products (AGE) play a causative role in the development of aberrant phenotypes of intraglomerular mesangial cells, contributing to acute/chronic glomerulonephritis. The aim of this study was to explore mechanistic effects of the flavonoid chrysin present in bee propolis and herbs on actin dynamics, focal adhesion, and the migration of AGE-exposed mesangial cells. The in vitro study cultured human mesangial cells exposed to 33 mM glucose and 100 μg/mL AGE-bovine serum albumin (AGE-BSA) for up to 5 days in the absence and presence of 1–20 μM chrysin. The in vivo study employed db/db mice orally administrated for 10 weeks with 10 mg/kg chrysin. The presence of ≥10 μM chrysin attenuated mesangial F-actin induction and bundle formation enhanced by AGE. Chrysin reduced the mesangial induction of α-smooth muscle actin (α-SMA) by glucose, and diminished the tissue α-SMA level in diabetic kidneys, indicating its blockade of mesangial proliferation. The treatment of chrysin inhibited the activation of vinculin and paxillin and the induction of cortactin, ARP2/3, fascin-1, and Ena/VASP-like protein in AGE-exposed mesangial cells. Oral administration of chrysin diminished tissue levels of cortactin and fascin-1 elevated in diabetic mouse kidneys. Mesangial cell motility was enhanced by AGE, which was markedly attenuated by adding chrysin to cells. On the other hand, chrysin dampened the induction of autophagy-related genes of beclin-1, LC3 I/II, Atg3, and Atg7 in mesangial cells exposed to AGE and in diabetic kidneys. Furthermore, chrysin reduced the mTOR activation in AGE-exposed mesangial cells and diabetic kidneys. The induction of mesangial F-actin, cortactin, and fascin-1 by AGE was deterred by the inhibition of autophagy and mTOR. Thus, chrysin may encumber diabetes-associated formation of actin bundling and focal adhesion and mesangial cell motility through disturbing autophagy and mTOR pathway.

Mass spectrometry-based circulating IgA1 complexes screening driven identification of IgA-alpha-1-microglobulin complex in IgA nephropathy

2020 ◽  
Author(s):  
Boyang Xu ◽  
Li Zhu ◽  
Qingsong Wang ◽  
Yanfeng Zhao ◽  
Meng Jia ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Iga Nephropathy ◽  
Cell Injury ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Independent Population ◽  
Tubulointerstitial Lesions ◽  
Noninvasive Biomarker

Abstract Background IgA nephropathy (IgAN) is characterized by predominant IgA deposition in the glomerular mesangium. Previous studies proved that renal-deposited IgA in IgAN came from circulating IgA1-containing complexes (CICs). Methods To explore the composition of CICs in IgAN, we isolated CICs from IgAN patients and healthy controls, and then quantitatively analyzed them by mass spectrometry. Meanwhile, the isolated CICs were used to treat human mesangial cells to monitor mesangial cell injury. Taken together the proteins content and injury effects, the key constituent in CICs was identified. Then, the circulating levels of identified key constituent-IgA complex were detected in an independent population by an in-house-developed ELISA. Results By comparing the proteins of CICs between IgAN patients and controls, we found that 14 proteins showed significantly different levels. Among them, alpha-1-microglobulin content in CICs was associated with not only in vitro mesangial cell proliferation and MCP-1 secretion but also in vivo eGFR levels and tubulointerstitial lesions in IgAN patients. Moreover, we found alpha-1-microglobulin was prone to bind aberrant glycosylated IgA1. Additionally, an elevated circulating IgA-alpha-1-microglobulin complex levels were detected in an independent IgAN population, and IgA-alpha-1-microglobulin complex levels were correlated with hypertension, eGFR levels and Oxford-T scores in these IgAN patients. Conclusions Our results suggest that the IgA-alpha-1-microglobulin complex is an important constituent in CICs, and that circulating IgA-alpha-1-microglobulin complex detection might serve as a potential noninvasive biomarker detection method for IgAN.

scholarly journals Differential trafficking of albumin and IgG facilitated by the neonatal Fc receptor in podocytes in vitro and in vivo.

2018 ◽  
Author(s):  
James Dylewski ◽  
Evgenia Dobrinskikh ◽  
Linda Lewis ◽  
Pantipa Tonsawan ◽  
Parmjit Jat ◽  
...  
Keyword(s):  
Plasma Proteins ◽  
Serum Proteins ◽  
Mesangial Cells ◽  
Smooth Muscle Actin ◽  
Fc Receptor ◽  
Neonatal Fc Receptor ◽  
Kidney Disease Progression

Proteinuria is strongly associated with kidney disease progression but the mechanisms underlying podocyte handling of serum proteins such as albumin and IgG remain to be elucidated. We have previously shown that albumin and IgG are transcytosed by podocytes in vitro. In other epithelial cells, the neonatal Fc receptor (FcRn) is required to salvage albumin and IgG from the degradative pathway thereby allowing these proteins to be transcytosed or recycled. Here we directly examine the role of FcRn in albumin and IgG trafficking in podocytes by studying handling of these proteins in FcRn knockout (KO) podocytes in vitro and in a podocyte-specific FcRn knockout mice in vivo. In vitro, we find that knockout of FcRn leads to IgG accumulation in podocytes but does not alter albumin trafficking. Similarly, in vivo, podocyte-specific knockout of FcRn does not result in albumin accumulation in podocytes in vivo as measured by mean albumin fluorescence intensity whereas these mice demonstrate significant intraglomerular accumulation of IgG over time. In addition we find that podocyte-specific FcRn KO mice demonstrate mesangial expansion as they age and activation of mesangial cells as demonstrated by increased expression of ?-smooth muscle actin. Taken together, these results suggest that trafficking pathways for albumin and IgG differ in podocytes and that sustained disruption of trafficking of plasma proteins alters glomerular structure.

scholarly journals Enhanced expression of selenocysteine lyase in acute glomerulonephritis and its regulation by AP-1

2006 ◽  
Vol 11 (3) ◽  
Author(s):  
Claudia Jafari ◽  
Ulf Panzer ◽  
Oliver Steinmetz ◽  
Gunther Zahner ◽  
Rolf Stahl ◽  
...  
Keyword(s):  
Mesangial Cells ◽  
Regulatory Region ◽  
Feedback Mechanism ◽  
Luciferase Expression ◽  
Chronic Glomerulonephritis ◽  
Acute Glomerulonephritis ◽  
Enhancer Element ◽  
Selenocysteine Lyase

AbstractAcute glomerulonephritis can lead to chronic glomerulonephritis or resolve without permanent damage to the kidneys. Differential gene expression was studied in a model of acute and chronic glomerulonephritis to identify factors influencing the course of glomerulonephritis towards healing or chronification. One of the differentially expressed genes was identified as SCL, encoding selenocysteine lyase. Its expression was higher in acute glomerulonephritis and lower in chronic glomerulonephritis. The transcriptional regulation of SCL was studied in vitro in rat mesangial cells (MC). SCL RNA expression increased eight-fold compared to the baseline after stimulation with interleukin-1β (IL-1β) for three hours. Luciferase expression and gel shift experiments revealed an enhancer element between bp −152 and −298 of the SCL 5’-regulatory region, with protein binding to an AP-1 binding site that may be involved in the regulation of SCL-RNA in vivo in an endogenous feedback mechanism to the inflammatory reaction in acute glomerulonephritis, leading to resolution of this disease.

scholarly journals Endothelium-derived relaxing factor, nitric oxide: effects on and production by mesangial cells and the glomerulus.

1993 ◽  
Vol 3 (8) ◽  
pp. 1435-1441
Author(s):  
L Raij ◽  
P J Shultz
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

The endothelium-derived relaxing factor nitric oxide (EDRF/NO) is a labile, endogenous vasodilator that is important in the control of systemic vascular tone. This review focuses on the effects of EDRF/NO on glomerular mesangial cells in vitro and on the role of EDRF/NO in mesangial and glomerular physiology and pathophysiology in vivo. It was concluded that EDRF/NO can stimulate increases in cGMP, inhibit mesangial cell contraction, and inhibit growth factor-induced proliferation of mesangial cells in culture. Furthermore, incubation with endotoxin or cytokines stimulates mesangial cells to produce EDRF/NO, via an inducible NO synthase enzyme. Therefore, it is likely that NO could play a role in the inflammatory response within the glomerulus. Finally, recent studies providing evidence that EDRF/NO is functional within the glomerulus in vivo, especially during endotoxemia and inflammation are also reviewed.

scholarly journals Catecholamines production by kidney tissue and mesangial cell culture is differentially modulated by diabetes

2021 ◽  
Author(s):  
Roseli Peres Moreira ◽  
Nadia S. C. Bertoncello ◽  
Juliana Almada Colucci ◽  
Danielle Yuri Arita ◽  
Maria Claudina Camargo de Andrade ◽  
...  
Keyword(s):  
Cell Culture ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Kidney Tissue ◽  
International Diabetes Federation ◽  
Sharp Decrease ◽  
Diabetic Rats ◽  
Control Group

Abstract Introduction: According to the International Diabetes Federation, the number of people with diabetes mellitus may reach 700 million in 2045. Catecholamines are involved in the regulation of several kidney functions. This study investigates the effects of hyperglycemia on catecholamines' metabolism in kidney tissue from control, diabetic, and insulin-treated diabetic rats, both in vivo and in vitro. Methods: Male Wistar-Hannover rats were randomized into: control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by a single injection of streptozotocin, and diabetic treated group also received insulin. After 60 days, blood and kidney tissue from all groups were collected for catecholamines' quantification and mesangial cells culture. Results: diabetic rats had lower body weight, hyperglycemia, and increase water intake and diuresis. Additionally, diabetes promoted a sharp decrease in creatinine clearance compared to control group. Regarding the whole kidney extracts, both diabetic groups (treated and non-treated) had significant reduction in norepinephrine concentration. In mesangial cell culture, catecholamines' concentration were lower in the culture medium than in the intracellular compartment for all groups. Norepinephrine, epinephrine, and dopamine medium levels were increased in the diabetic group. Conclusion: The major finding of the present study was that 8 weeks of diabetes induction altered the kidney catecholaminergic system in a very specific manner, once the production of catecholamines in the excised kidney tissue from diabetic rats was differentially modulated as compared with the production and secretion by cultured mesangial cells.

scholarly journals Rat mesangial cells express macrophage migration inhibitory factor in vitro and in vivo.

1998 ◽  
Vol 9 (3) ◽  
pp. 417-424
Author(s):  
G H Tesch ◽  
D J Nikolic-Paterson ◽  
C N Metz ◽  
W Mu ◽  
M Bacher ◽  
...  
Keyword(s):  
Growth Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Mesangial Cell ◽  
De Novo ◽  
Mesangial Cells ◽  
Macrophage Migration ◽  
Mrna And Protein Expression ◽  
Macrophage Accumulation

Mesangial cells are thought to promote glomerular macrophage accumulation in glomerulonephritis. This may occur through the production of macrophage migration inhibitory factor (MIF), a molecule known to regulate macrophage accumulation at sites of inflammation. To study this, glomerular MIF expression and macrophage accumulation were examined in rat anti-Thy-1 disease, a model of mesangioproliferative nephritis. In situ hybridization and immunohistochemistry showed that MIF is expressed by some podocytes in normal rat glomeruli. De novo MIF expression by glomerular endothelium was seen on day 1 of anti-Thy-1 disease. On day 6, glomerular MIF mRNA and protein expression were prominent in segmental proliferative lesions, which was also the location of most infiltrating macrophages. Double-staining identified de novo MIF mRNA and protein expression by proliferating mesangial cells within these lesions. Cytokine regulation of mesangial cell MIF expression was examined in vitro. Northern blotting showed that cultured rat mesangial cells express a single 0.6-kb species of MIF mRNA, and Western blotting detected a single protein band of 12.5 kD. Six-hour stimulation of mesangial cells with interferon-gamma or platelet-derived growth factor significantly increased MIF mRNA levels. However, the addition of recombinant MIF to mesangial cells did not affect mesangial cell proliferation or constitutive transforming growth factor-beta mRNA expression, nor did MIF induce monocyte chemoattractant protein-1 mRNA expression. In conclusion, this is the first study to demonstrate that mesangial cells can produce MIF in vivo and in vitro. It is postulated that mesangial cell MIF production in response to injury acts to promote macrophage accumulation within segmental proliferative lesions in rat anti-Thy-1 nephritis.

scholarly journals Macromolecular properties that promote mesangial binding and mesangiopathic nephritis.

1992 ◽  
Vol 2 (10) ◽  
pp. S149 ◽  
Author(s):  
S N Emancipator ◽  
C S Rao ◽  
A Amore ◽  
R Coppo ◽  
J G Nedrud
Keyword(s):  
Cell Surface ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Sendai Virus ◽  
Cell Metabolism ◽  
Immunoglobulin A ◽  
Cross Linking ◽  
The Matrix

The hydrodynamic size, electrostatic charge, and specificity are established determinants of the site of glomerular localization of macromolecules. Larger macromolecules or aggregates and anionic charge are associated with mesangial deposits, despite the fact that the mesangial matrix bears a negative charge similar to that of the capillary wall. Antigens such as Sendai virus, a model infectious pathogen, gliadin, a model dietary/environmental agent and fibronectin, a model endogenous macromolecule, bind to mesangial cells in vitro on the basis of cell surface glycoconjugates. Nonantibody immunoglobulin A, which does not bind to cells directly, binds to these elements via different carbohydrate specificities (simple sugar inhibition). Such binding promotes or augments macromolecular deposition in the mesangium. More significantly, mesangial deposits per se are not pathogenic, because normal renal function can be observed with florid deposits. Pathogenic deposits must have properties that alter mesangial cell metabolism or interaction with the matrix. Although complement activation is well recognized, complement-independent mechanisms related to cell surface modulation are being recognized. In vitro, antigen/immunoglobulin A aggregates alter mesangial cell eicosanoid synthesis. In vivo, large-lattice cross-linking by particulate antigen promotes hematuria. We conclude that the binding of macromolecules to cells and the cross-linking of cell surface molecules cause alterations in the mesangial cells and therefore in glomerular function. The mesangial cell, rather than a passive respondent, is an active participant in the genesis of glomerulonephritis.

scholarly journals Mycophenolic acid: a new approach to the therapy of experimental mesangial proliferative glomerulonephritis.

1998 ◽  
Vol 9 (11) ◽  
pp. 2055-2066 ◽  
Author(s):  
R Ziswiler ◽  
K Steinmann-Niggli ◽  
A Kappeler ◽  
C Daniel ◽  
H P Marti
Keyword(s):  
Mycophenolic Acid ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Smooth Muscle Actin ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
New Approach ◽  
Matrix Deposition ◽  
Renal Histology

Mycophenolate mofetil (MMF) represents a powerful immunosuppressant in organ transplantation. The aim of this study was to determine the anti-inflammatory effects of MMF on mesangial cells. Cultured rat mesangial cells were exposed to mycophenolic acid (MPA) in concentrations of 0.1 to 10 microM. MPA inhibited the proliferation of these cells in a dose-dependent manner. A maximum of 98% inhibition was obtained by a 2-d exposure of mesangial cells to > or =5 microM MPA. As expected, the addition of > or =75 microM guanosine prevented the antiproliferative effect of MPA completely. Subsequently, in vivo studies were performed in the anti-Thy1.1 nephritis model. Sixty-six male Wistar rats were investigated: healthy rats (n = 15), treated healthy rats (n = 6), nephritic rats (n = 15), and treated nephritic rats (n = 30). MMF therapy (40 mg/kg body wt per d) of nephritic animals was initiated 2 d before (n = 3) and 6 h (n = 15) or 2 d (n = 12) after induction of nephritis. Renal histology was analyzed at days +6 and +9 after initiation of disease. Therapy of nephritic rats by MMF resulted in a significant amelioration of glomerular histology, assessed by glomerular cellularity, synthesis of alpha-smooth muscle actin, extracellular matrix deposition, and glomerular hypertrophy. Proteinuria, expressed as areas under the curve of protein/creatinine ratios versus time, showed a clear tendency toward a reduction by MMF therapy. Healthy control rats were not negatively affected by exposure to MMF. In summary, this study shows that mesangial cell proliferation can be significantly inhibited by MPA in vitro and in vivo. MMF represents a new approach to the therapy of experimental mesangial cell-mediated forms of glomerulonephritis.

scholarly journals The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zhang ◽  
Zhaohui Zhong ◽  
Mei Li ◽  
Jingyi Chen ◽  
Tingru Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
The Cancer Genome Atlas ◽  
Actin Dynamics ◽  
Elevated Expression ◽  
Sw480 Cells ◽  
And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models

2021 ◽  
pp. 153473462110021
Author(s):  
Joon M. Jung ◽  
Hae K. Yoon ◽  
Chang J. Jung ◽  
Soo Y. Jo ◽  
Sang G. Hwang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Plasma Treatment ◽  
Cold Plasma ◽  
Smooth Muscle Actin ◽  
Treated Group ◽  
Control Group ◽  
Alpha Smooth Muscle Actin ◽  
Skin Wound Healing

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

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