scholarly journals Huoxue Jiedu Huayu Recipe Ameliorates Mesangial Cell Pyroptosis in Contralateral Kidney of UUO Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yuxuan Zhang ◽  
Juan Hao ◽  
Xuelian Ma ◽  
Qiyue Zhao ◽  
Xiaomeng Gao ◽  
...  
Keyword(s):  
Mesangial Cell ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Sprague Dawley ◽  
Human Mesangial Cells ◽  
Left Ureter ◽  
Contralateral Kidney ◽  
Pyrin Domain ◽  
Sprague Dawley Rats ◽  
Associated Proteins

Objectives. To observe the effects of the Huoxue Jiedu Huayu Recipe (HJHR) on pyroptosis of glomerular mesangial cells in the contralateral unobstructed kidney (CK) of unilateral ureteral obstruction (UUO) rats. Methods. Sprague-Dawley rats were randomly divided into 4 groups: sham group, UUO group (10 days of left ureter ligation), UUO treated with eplerenone (EPL) (UUO + EPL) group, and UUO treated with HJHR (UUO + HJHR) group. The CKs of all rats were collected for studies. Results. Cell pyroptosis and macrophage infiltration was found in contralateral glomeruli, and nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) and interleukin (IL)-1β expression was upregulated in the CK of UUO rats. All of these changes were inhibited by HJHR and eplerenone. To determine how aldosterone (Aldo) activated the mineralocorticoid receptor (MR) and then induced mesangial cell pyroptosis with NLRP3-caspase-1-IL-1β pathway, human mesangial cells (HMCs) were treated with HJHR and eplerenone, which were examined to detect the expression of NLRP3 inflammasome-associated proteins following treatment with Aldo. Conclusion. These results suggest that HJHR and eplerenone suppressed HMC pyroptosis via the MR/NLRP3 pathway.

A mechanism by which atrial natriuretic factor mediates its glomerular actions

1986 ◽  
Vol 251 (6) ◽  
pp. F1036-F1042 ◽  
Author(s):  
R. G. Appel ◽  
J. Wang ◽  
M. S. Simonson ◽  
M. J. Dunn
Keyword(s):  
Mesangial Cell ◽  
Mesangial Cells ◽  
Dependent Manner ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Sprague Dawley ◽  
Cell Contraction ◽  
Concentration Dependent Manner ◽  
Cell Contractility

Differential in vivo glomerular effects of atriopeptin I (AP I) and atriopeptin III (AP III) were studied in parallel with in vitro physiological and biochemical parameters. In anesthetized Sprague-Dawley rats, AP III, but not AP I, significantly increased glomerular filtration rate. Image analysis microscopy was used to assess the effect of AP I and AP III on angiotensin II (ANG II)-induced contraction of cultured rat glomerular mesangial cells. AP III, but not AP I, inhibited ANG II-induced mesangial cell contraction in a concentration-dependent manner. Additional inhibitory agents included exogenous DBcGMP, 8-BrcGMP, Na nitroprusside, and DBcAMP. AP III stimulated mesangial cell cGMP with a lower threshold and greater maximum stimulation than AP I. Neither agent stimulated cAMP accumulation. Since mesangial cell contractility may regulate the glomerular capillary surface area, these results suggest that AP III partially mediates its glomerular effects through inhibition of ANG II-induced mesangial cell contraction. Whereas cGMP is not clearly implicated as the mediator of this effect, it appears that both cGMP and cAMP may regulate the state of mesangial cell contractility.

Evidences for the phagocytic activity of cultured rat mesangial cells

1990 ◽  
Vol 48 (3) ◽  
pp. 326-327
Author(s):  
Katsuyoshi Kouda ◽  
Masato Imada ◽  
Yoshio Igarashi ◽  
Akira Yamashita
Keyword(s):  
Phagocytic Activity ◽  
Fetal Calf Serum ◽  
Renal Cortex ◽  
Mesangial Cells ◽  
Calf Serum ◽  
Immunohistochemical Method ◽  
Glomerular Mesangial Cells ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

It is known that glomerular mesangial cells have two major functions; the control of glomerular blood flow by contraction and the removal of macromolecules from the mesangial region by the endocytosis. As regards the latter function, the evidence of phagocytic activity for particulate materials is controversial. In this study, we attempted to make it clear whether mesangial cells isolated from glomeruli exhibit phagocytic activity in vitro.Male Sprague-Dawley rats, 6-8 wk old, were used. Glomeruli were isolated from rat renal cortex by the sieving technique according to Morita. The isolated glomeruli were cultured at 37°C in an atmosphere of 95% air, 5% CO2 in a medium containing 5ml of RPMI-1640 with 20% decomplemented fetal calf serum, and subcultured. Mesangial cells purified at the 6-20th succesive cultivations were identified by their morphology and antigenic phenotypes which were analyzed by immunohistochemical method using anti Thy-1, anti Ia, anti leukocyte common(LC) antigen, anti iC3bR, and Mar(anti rat macrophage antigen) 1-4 monoclonal antibodies. Fc receptor was detected with rosette forming method using sheep blood cells(SRBC).

scholarly journals Expression of extracellular matrix molecules in human mesangial cells in response to prolonged hyperglycaemia

1996 ◽  
Vol 316 (3) ◽  
pp. 985-992 ◽  
Author(s):  
Nadia Abdel WAHAB ◽  
Katherine HARPER ◽  
Roger M. MASON
Keyword(s):  
Cell Cultures ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Dermal Fibroblasts ◽  
Rt Pcr ◽  
Collagen Types ◽  
Human Mesangial Cells ◽  
Core Proteins ◽  
Cell Layers ◽  
Tgf Β1

Post-mitotic cultures of human mesangial cells were maintained in media containing 4–30 mM D-glucose for up to 28 days. Changes in mRNA and protein levels for specific macromolecules occurred between 7 and 14 days after initiating hyperglycaemic conditions. Slot blot analysis showed 2–3-fold increases in mRNAs for collagen type I, fibronectin, versican and perlecan, whereas mRNA for decorin was increased by up to 20-fold. Levels of mRNAs for biglycan and syndecan were unaffected by hyperglycaemic culture. Reverse transcriptase PCR (RT–PCR) confirmed that decorin mRNA levels are greatly elevated and also showed increased transcription of the TGF-β1 gene in hyperglycaemic cultures. Western analysis and ELISA indicated accumulations of collagen types I and III, laminin and fibronectin in the cell layers and media of hyperglycaemic cultures with increasing time. Type IV collagen did not accumulate in either compartment of hyperglycaemic mesangial cell cultures. Collagen types I, III, and fibronectin did not accumulate in the cell layers of hyperglycaemic human dermal fibroblasts, indicating a cell-specific response in mesangial cultures. Decorin and versican, but not biglycan, were increased in the hyperglycaemic mesangial cell culture media. There were no apparent changes in core proteins for decorin and biglycan in fibroblast media. Transforming growth factor β1 (TGF-β1) in hyperglycaemic mesangial cell cultures increased 5-fold after 7 days, but decreased thereafter to only approx. 2-fold after 28 days. The changes in TGF-β1 mRNA, as detected by RT–PCR, and protein followed one another closely.

scholarly journals Tumor necrosis factor alpha activates soluble guanylate cyclase in bovine glomerular mesangial cells via an L-arginine-dependent mechanism.

1990 ◽  
Vol 172 (6) ◽  
pp. 1843-1852 ◽  
Author(s):  
P A Marsden ◽  
B J Ballermann
Keyword(s):  
Guanylate Cyclase ◽  
Mesangial Cell ◽  
Soluble Guanylate Cyclase ◽  
Mesangial Cells ◽  
Tnf Alpha ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Concentration Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Factor Alpha

Endothelium-derived nitric oxide (NO) causes vasodilatation by activating soluble guanylate cyclase, and glomerular mesangial cells respond to NO with elevations of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We explored whether mesangial cells can be stimulated to produce NO and whether NO modulates mesangial cell function in an autocrine or paracrine fashion. Tumor necrosis factor alpha (TNF-alpha) raised mesangial cell cGMP levels in a time- and concentration-dependent manner (threshold dose 1 ng/ml, IC50 13.8 ng/ml, maximal response 100 ng/ml). TNF-alpha-induced increases in mesangial cGMP content were evident at 8 h and maximal at 18-24 h. The TNF-alpha-induced stimulation of mesangial cell cGMP production was abrogated by actinomycin D or cycloheximide suggesting dependence on new RNA or protein synthesis. Hemoglobin and methylene blue, both known to inhibit NO action, dramatically reduced TNF-alpha-induced mesangial cell cGMP production. Superoxide dismutase, known to potentiate NO action, augmented the TNF-alpha-induced effect. Ng-monomethyl-L-arginine (L-NMMA) decreased cGMP levels in TNF-alpha-treated, but not vehicle-treated mesangial cells in a concentration-dependent manner (IC50 53 microM). L-arginine had no effect on cGMP levels in control or TNF-alpha-treated mesangial cells but reversed L-NMMA-induced inhibition. Interleukin 1 beta and lipopolysaccharide (LPS), but not interferon gamma, also increased mesangial cell cGMP content. Transforming growth factor beta 1 blunted the mesangial cell response to TNF-alpha. TNF-alpha-induced L-arginine-dependent increases in cGMP were also evident in bovine renal artery vascular smooth muscle cells, COS-1 cells, and 1502 human fibroblasts. These findings suggest that TNF-alpha induces expression in mesangial cell of an enzyme(s) involved in the formation of L-arginine-derived NO. Moreover, the data indicate that NO acts in an autocrine and paracrine fashion to activate mesangial cell soluble guanylate cyclase. Cytokine-induced formation of NO in mesangial and vascular smooth muscle cells may be implicated in the pathogenesis of septic shock.

Mesangial cells express PDGF mRNAs and proliferate in response to PDGF

1988 ◽  
Vol 255 (4) ◽  
pp. F674-F684 ◽  
Author(s):  
P. J. Shultz ◽  
P. E. DiCorleto ◽  
B. J. Silver ◽  
H. E. Abboud
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Northern Blot Analysis ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Human Mesangial Cells ◽  
Human Foreskin Fibroblasts ◽  
Human Glomerular Mesangial Cells ◽  
Paracrine Growth Factor

Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin and is released and/or synthesized by platelets, macrophages, endothelial cells, and rat mesangial cells. In the present investigation, we found that human glomerular mesangial cells in culture release a PDGF-like protein which competes for 125I-PDGF binding to human foreskin fibroblasts and is mitogenic for these fibroblasts. The competing and to a lesser extent the mitogenic activities present in the conditioned medium are partially recognized by an anti-PDGF antibody. Northern blot analysis of poly(A)+ RNA from human mesangial cells demonstrates the expression of both PDGF A- and B-chain mRNAs. PDGF also binds to mesangial cells in a specific manner and stimulates DNA synthesis and cell proliferation. These data suggest that a PDGF-like protein secreted by mesangial cells or released from platelets, monocytes, or endothelial cells during glomerular inflammation may function as an autocrine or a paracrine growth factor for these cells. The biological role of PDGF in mediating proliferative and other inflammatory events in the glomerulus remains to be identified.

scholarly journals TGFβ acts through PDGFRβ to activate mTORC1 via the Akt/PRAS40 axis and causes glomerular mesangial cell hypertrophy and matrix protein expression

2020 ◽  
Vol 295 (42) ◽  
pp. 14262-14278
Author(s):  
Soumya Maity ◽  
Falguni Das ◽  
Balakuntalam S. Kasinath ◽  
Nandini Ghosh-Choudhury ◽  
Goutam Ghosh Choudhury
Keyword(s):  
Growth Factor ◽  
Matrix Protein ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Kidney Cortex ◽  
Glomerular Mesangial Cells ◽  
Cell Hypertrophy ◽  
Tgfβ Receptor ◽  
Mtorc1 Activation ◽  
Noncanonical Signaling

Interaction of transforming growth factor-β (TGFβ)-induced canonical signaling with the noncanonical kinase cascades regulates glomerular hypertrophy and matrix protein deposition, which are early features of glomerulosclerosis. However, the specific target downstream of the TGFβ receptor involved in the noncanonical signaling is unknown. Here, we show that TGFβ increased the catalytic loop phosphorylation of platelet-derived growth factor receptor β (PDGFRβ), a receptor tyrosine kinase expressed abundantly in glomerular mesangial cells. TGFβ increased phosphorylation of the PI 3-kinase–interacting Tyr-751 residue of PDGFRβ, thus activating Akt. Inhibition of PDGFRβ using a pharmacological inhibitor and siRNAs blocked TGFβ-stimulated phosphorylation of proline-rich Akt substrate of 40 kDa (PRAS40), an intrinsic inhibitory component of mTORC1, and prevented activation of mTORC1 in the absence of any effect on Smad 2/3 phosphorylation. Expression of constitutively active myristoylated Akt reversed the siPDGFRβ-mediated inhibition of mTORC1 activity; however, co-expression of the phospho-deficient mutant of PRAS40 inhibited the effect of myristoylated Akt, suggesting a definitive role of PRAS40 phosphorylation in mTORC1 activation downstream of PDGFRβ in mesangial cells. Additionally, we demonstrate that PDGFRβ-initiated phosphorylation of PRAS40 is required for TGFβ-induced mesangial cell hypertrophy and fibronectin and collagen I (α2) production. Increased activating phosphorylation of PDGFRβ is also associated with enhanced TGFβ expression and mTORC1 activation in the kidney cortex and glomeruli of diabetic mice and rats, respectively. Thus, pursuing TGFβ noncanonical signaling, we identified how TGFβ receptor I achieves mTORC1 activation through PDGFRβ-mediated Akt/PRAS40 phosphorylation to spur mesangial cell hypertrophy and matrix protein accumulation. These findings provide support for targeting PDGFRβ in TGFβ-driven renal fibrosis.

The Actions of C-Type Natriuretic Peptide on Human Mesangial Cell Apoptosis and P53 Expression

2000 ◽  
Vol 6 (S2) ◽  
pp. 624-625
Author(s):  
K. Seta ◽  
C. Wei
Keyword(s):  
Receptor Antagonist ◽  
Natriuretic Peptide ◽  
Cell Apoptosis ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Endocrine System ◽  
P53 Gene ◽  
Glomerular Mesangial Cells ◽  
P53 Expression ◽  
Human Mesangial Cell

C-type natriuretic peptide (CNP) of endothelial cell origin via NPR-B receptor mediates antimitogenic and vasodilatory actions. As a circulating endocrine system, CNP plays a fundamental role in cardiorenal regulation. However, the actions of CNP on renal mesangial cell apoptosis remain poorly defined. Apoptosis might plays an important role during development of renal glomerular mesangial cells pathophysiology. The mechanisms of apoptosis include p53-dependent pathway and p53-independent pathway.The hypothesis of this study is that CNP induces apoptosis through the process involving p53 gene in human glomerular mesangial cells via natriuretic peptide biological receptor. Therefore, the current study was designed to investigate the effects of CNP on apoptosis and p53 expression in human mesangial cell in the absence or presence of CNP biological receptor antagonist.Cultured human mesangial cells (Clontech Lab., San Diego, CA) was incubated for 24 hours in the absence or presence of CNP (10-7 M). These studies were repeated with HS 142-1 (HS, 10-5 M), a CNP biological receptor antagonist.

Regulation of mesangial cell cyclooxygenase synthesis by cytokines and glucocorticoids

1992 ◽  
Vol 263 (1) ◽  
pp. F97-F102 ◽  
Author(s):  
D. W. Coyne ◽  
M. Nickols ◽  
W. Bertrand ◽  
A. R. Morrison
Keyword(s):  
Time Course ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Cell Types ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Prostaglandin Production ◽  
Arachidonate Release ◽  
Necrosis Factor

The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), potently induce prostaglandin formation in glomerular mesangial cells. Mechanisms by which these cytokines stimulate prostaglandin formation vary among cell types. We investigated whether alterations in phospholipase A2 (PLA2) or cyclooxygenase (COX) mass and activity contribute to the changes in mesangial cell prostaglandin production. These cytokines induced COX activity and mass in a time-dependent manner, which paralleled prostaglandin production. IL-1 increased COX mass approximately threefold by 24 h. TNF had a much smaller effect, although it appeared to be additive with IL-1. IL-1-induced COX mass was maintained at an increased level for at least 48 h. The glucocorticoid dexamethasone (DEX) virtually abolished prostaglandin production and blocked cytokine induction of COX activity and mass. DEX did not reduce COX activity or mass below the basal, serum-fed levels, however. By utilizing stable isotope methods, we could demonstrate that IL-1 increased free arachidonate levels, implying new PLA2 synthesis over a time course that was maximal at 6 h and was cycloheximide and actinomycin D sensitive. These data demonstrate that the cytokines IL-1 and TNF enhance synthesis of COX and PLA2, contributing to increased prostaglandin production. Cytokine-stimulated prostaglandin production ceases when cells are also treated with DEX, although control levels of COX activity and mass remain. This occurs because DEX inhibits the IL-1-induced enhanced arachidonate release.

Immune complex activation of rat glomerular mesangial cells: dependence on the Fc region of antibody

1989 ◽  
Vol 257 (3) ◽  
pp. F478-F485
Author(s):  
T. C. Knauss ◽  
P. Mene ◽  
S. A. Ricanati ◽  
M. Kester ◽  
G. R. Dubyak ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Inositol Phosphates ◽  
Exchange Chromatography ◽  
Water Soluble ◽  
Free Calcium ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Cross Sectional

Glomerulonephritis is frequently associated with immunoglobulin deposition in the mesangium. We had previously shown that contractile, rat mesangial cells in culture synthesize superoxide anion after binding immune complexes (IC) in a manner dependent on the Fc region of immunoglobulin G (IgG). We now studied the effects of soluble IC on mesangial cell cytosolic free calcium ([Ca2+]i) and phosphatidylinositol turnover as putative mechanisms of transmembrane signaling as well as prostaglandin biosynthesis and contraction. IC (500 micrograms specific antibody) raised [Ca2+]i in mesangial cells loaded with fura-2 from resting levels of 100.4 +/- 8.0 to a peak of 282.3 +/- 31.5 nM in a dose-dependent manner. Removal of extracellular Ca2+ by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid only slightly reduced peak, IC-stimulated [Ca2+]i to 236 +/- 18 nM but prevented the sustained phase of the response, indicating that IC both mobilized Ca2+ from intracellular stores and increased the influx of Ca2+ across the plasma membrane. IC did not increase water-soluble inositol phosphates, measured by anion-exchange chromatography of trichloroacetic acid-extracted cells but markedly stimulated PGE2 and thromboxane B2 synthesis in a dose- and time-dependent manner. Finally, IC (250 micrograms specific antibody) induced 45.8 +/- 10.1% of the cells to contract with an average decrease in cross-sectional surface area of 20.0 +/- 1.8% of basal as assessed by image-analysis microscopy. IC formed with F(ab')2 fragments of antibody and antigen or mixtures of antigen and nonimmune whole molecule antibody did not alter [Ca2+]i, induce prostaglandin synthesis, or stimulate mesangial cell contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Mesangial cell proteoglycans: synthesis and metabolism.

1992 ◽  
Vol 2 (10) ◽  
pp. S88
Author(s):  
M Davies ◽  
G J Thomas ◽  
L D Shewring ◽  
R M Mason
Keyword(s):  
Culture Medium ◽  
Mesangial Cell ◽  
Dermatan Sulfate ◽  
Mesangial Cells ◽  
Core Protein ◽  
Glomerular Mesangial Cells ◽  
Cellular Processes ◽  
Specialized Function ◽  
In Cells

In cultures of human adult glomerular mesangial cells, large chondroitin sulfate proteoglycans (CSPG) and small dermatan sulfate proteoglycans (DSPG) are synthesized. The large CSPG has a core protein, M(r) of 400,000 (major) and M(r) of 500,000 (minor), and binds to hyaluronic acid to form large aggregates. The two small DSPGs (Mr of approximately 350,000 and M(r) of approximately 200,000) were related to biglycan and decorin, respectively. The majority of these proteoglycans were located in the culture medium, but a hydrophobic form of the CSPG was extracted from the cell layer. Mesangial cells in the growing phase synthesized and secreted all three types of proteoglycans, but in cells arrested in G0 by serum deprivation the incorporation of (35S)sulfate in CSPG was drastically reduced. In the same cells stimulated to proliferate by replacing the medium with one containing serum, the synthesis of CSPG dramatically enhanced. The synthesis of CSPG and DSPG was also elevated in cells cocultured with cytokines but in contrast was significantly reduced when cultured in medium containing hyperglycemic levels of glucose. Finally, preliminary experiments are reported that indicate that CSPG and DSPG bind to low-density lipoproteins in vitro. These observations suggest a possible specialized function for proteoglycans in cellular processes characteristic of glomerular disease.

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