scholarly journals Kidney Proximal Tubular Epithelial-Specific Overexpression of Netrin-1 Suppresses Inflammation and Albuminuria through Suppression of COX-2-Mediated PGE2 Production in Streptozotocin-Induced Diabetic Mice

2012 ◽  
Vol 181 (6) ◽  
pp. 1991-2002 ◽  
Author(s):  
Riyaz Mohamed ◽  
Calpurnia Jayakumar ◽  
Punithavathi V. Ranganathan ◽  
Vadivel Ganapathy ◽  
Ganesan Ramesh
Keyword(s):  
Pge2 Production ◽  
Diabetic Mice ◽  
Proximal Tubular ◽  
Cox 2

scholarly journals PP2 Ameliorates Renal Fibrosis by Regulating the NF-κB/COX-2 and PPARγ/UCP2 Pathway in Diabetic Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Jinying Wei ◽  
Xinna Deng ◽  
Yang Li ◽  
Runmei Li ◽  
Zhaohua Yang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Mesangial Cells ◽  
Tubulointerstitial Fibrosis ◽  
Glomerular Mesangial Cells ◽  
Diabetic Mice ◽  
Ucp2 Expression ◽  
Renal Tubulointerstitial Fibrosis ◽  
Proximal Tubular ◽  
Cox 2 ◽  
Geo Database

Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis in diabetic nephropathy (DN). We aimed to evaluate the effects of PP2 on renal fibrosis of DN. GSE33744 and GSE86300 were downloaded from the GEO database. Firstly, 839 DEGs were identified between nondiabetic and diabetic mice renal glomerular samples. COX-2 was selected to assess the effects of PP2 on renal glomerulosclerosis. In db/db mice, PP2 decreased the expression of COX-2, phosphorylated p65, and fibrotic proteins, accompanied with attenuated renal glomerulosclerosis. In cultured glomerular mesangial cells, high glucose- (HG-) induced p65 phosphorylation and COX-2 expression were attenuated by PP2 or NF-κB inhibitor PDTC. PP2, PDTC, or COX-2 inhibitor NS-398 ameliorated abnormal proliferation and expression of fibrotic proteins induced by HG. Secondly, 238 DEGs were identified between nondiabetic and diabetic mice renal cortex samples. UCP2 was selected to assess the effects of PP2 on renal tubulointerstitial fibrosis. In db/db mice, PP2 decreased the expression of PPARγ and UCP2, accompanied with attenuated renal tubulointerstitial fibrosis and EMT. In cultured proximal tubular cells, HG-induced PPARγ and UCP2 expression was inhibited by PP2 or PPARγ antagonist GW9662. PP2, GW9662, or UCP2 shRNA ameliorated HG-induced EMT. These results indicated that PP2 ameliorated renal fibrosis in diabetic mice.

scholarly journals Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Coral García-Pastor ◽  
Selma Benito-Martínez ◽  
Ricardo J. Bosch ◽  
Ana B. Fernández-Martínez ◽  
Francisco J. Lucio-Cazaña
Keyword(s):  
Hypoxia Inducible Factor ◽  
Renal Diseases ◽  
Prostaglandin E ◽  
Relevant Factor ◽  
Tubular Injury ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Cox 2 ◽  
Induced Apoptosis

AbstractProximal tubular cells (PTC) are particularly vulnerable to hypoxia-induced apoptosis, a relevant factor for kidney disease. We hypothesized here that PTC death under hypoxia is mediated by cyclo-oxygenase (COX-2)-dependent production of prostaglandin E2 (PGE2), which was confirmed in human proximal tubular HK-2 cells because hypoxia (1% O2)-induced apoptosis (i) was prevented by a COX-2 inhibitor and by antagonists of prostaglandin (EP) receptors and (ii) was associated to an increase in intracellular PGE2 (iPGE2) due to hypoxia-inducible factor-1α-dependent transcriptional up-regulation of COX-2. Apoptosis was also prevented by inhibitors of the prostaglandin uptake transporter PGT, which indicated that iPGE2 contributes to hypoxia-induced apoptosis (on the contrary, hypoxia/reoxygenation-induced PTC death was exclusively due to extracellular PGE2). Thus, iPGE2 is a new actor in the pathogenesis of hypoxia-induced tubular injury and PGT might be a new therapeutic target for the prevention of hypoxia-dependent lesions in renal diseases.

scholarly journals Bone Marrow Mesenchymal Stromal Cells on Silk Fibroin Scaffolds to Attenuate Polymicrobial Sepsis Induced by Cecal Ligation and Puncture

Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1433
Author(s):  
Ok-Hyeon Kim ◽  
Jun-Hyung Park ◽  
Jong-In Son ◽  
Ok-Ja Yoon ◽  
Hyun-Jung Lee
Keyword(s):  
Bone Marrow ◽  
Cecal Ligation ◽  
Biological Properties ◽  
Pge2 Production ◽  
Polymicrobial Sepsis ◽  
Control Surface ◽  
Related Factors ◽  
Cox 2 ◽  
Anti Inflammatory

Suitable scaffolds with appropriate mechanical and biological properties can improve mesenchymal stromal cell (MSC) therapy. Because silk fibroins (SFs) are biocompatible materials, they were electrospun and applied as scaffolds for MSC therapy. Consequently, interferon (IFN)-primed human bone marrow MSCs on SF nanofibers were administered into a polymicrobial sepsis murine model. The IL-6 level gradually decreased from 40 ng/mL at 6 h after sepsis to 35 ng/mL at 24 h after sepsis. The IL-6 level was significantly low as 5 ng/mL in primed MSCs on SF nanofibers, and 15 ng/mL in primed MSCs on the control surface. In contrast to the acute response, inflammation-related factors, including HO-1 and COX-2 in chronic liver tissue, were effectively inhibited by MSCs on both SF nanofibers and the control surface at the 5-day mark after sepsis. An in vitro study indicated that the anti-inflammatory function of MSCs on SF nanofibers was mediated through enhanced COX-2-PGE2 production, as indomethacin completely abrogated PGE2 production and decreased the survival rate of septic mice. Thus, SF nanofiber scaffolds potentiated the anti-inflammatory and immunomodulatory functions of MSCs, and were beneficial as a culture platform for the cell therapy of inflammatory disorders.

scholarly journals Regulation by Interleukin-10 and Interleukin-4 of Cyclooxygenase-2 Expression in Human Neutrophils

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1621-1628 ◽  
Author(s):  
Hiroaki Niiro ◽  
Takeshi Otsuka ◽  
Kenji Izuhara ◽  
Kunihiro Yamaoka ◽  
Koichi Ohshima ◽  
...  
Keyword(s):  
Early Stage ◽  
Interleukin 10 ◽  
Pge2 Production ◽  
Interleukin 4 ◽  
Human Neutrophils ◽  
Effector Cells ◽  
Proinflammatory Mediators ◽  
Healthy Donors ◽  
Cox 2 ◽  
Anti Inflammatory

Neutrophils are important effector cells of acute inflammation because of their potential capacity to synthesize various proinflammatory mediators, and inhibition of their production is expected to result in anti-inflammatory effects. In this study, we investigate the effects of the anti-inflammatory cytokines, interleukin-10 (IL-10) and IL-4, on prostanoid synthesis in human neutrophils. Neutrophils isolated from healthy donors constitutively produced a small amount of prostaglandin E2 (PGE2 ) without any stimulations, whereas they produced a large amount of PGE2 after lipopolysaccharide (LPS) stimulation. IL-10 and IL-4 selectively inhibited their LPS-induced PGE2 production. Inhibition by both cytokines occurred at an early stage of LPS stimulation. Anti–IL-10 treatment of LPS-stimulated neutrophils resulted in enhanced PGE2 production. LPS-induced PGE2 and thromboxane B2 (TXB2 ) production in aspirin-treated neutrophils was significantly inhibited by IL-10, IL-4, and NS-398. Moreover, IL-10 and IL-4 inhibited LPS-induced cyclooxygenase (COX) activity in neutrophils. Western blot and immunocytochemical analysis showed that COX-2 protein was clearly induced in LPS-stimulated neutrophils and that its induction was inhibited by both IL-10 and IL-4. Moreover, both of these cytokines inhibited COX-2 mRNA expression in LPS-stimulated neutrophils. These results raise the possibility that these two cytokines may both offer potent clinical utility as anti-inflammatory agents in the future.

scholarly journals Therapy with antisense TGF-β1 oligodeoxynucleotides reduces kidney weight and matrix mRNAs in diabetic mice

2000 ◽  
Vol 278 (4) ◽  
pp. F628-F634 ◽  
Author(s):  
Dong Cheol Han ◽  
Brenda B. Hoffman ◽  
Soon Won Hong ◽  
Jia Guo ◽  
Fuad N. Ziyadeh
Keyword(s):  
Proximal Tubule ◽  
High Glucose ◽  
Leucine Incorporation ◽  
Diabetic Mice ◽  
Renal Hypertrophy ◽  
Kidney Weight ◽  
Cell Hypertrophy ◽  
Proximal Tubular ◽  
Tgf Β1

Inhibition of gene expression by antisense oligodeoxynucleotides (ODNs) relies on their ability to bind complementary mRNA sequences and prevent translation. The proximal tubule is a suitable target for ODN therapy in vivo because circulating ODNs accumulate in the proximal tubule in high concentrations. Because increased proximal tubular transforming growth factor- β1 (TGF-β1) expression may mediate diabetic renal hypertrophy, we investigated the effects of antisense TGF-β1 ODN on the high-glucose-induced proximal tubular epithelial cell hypertrophy in tissue culture and on diabetic renal hypertrophy in vivo. Mouse proximal tubular cells grown in 25 mM d-glucose and exposed to sense ODN as control (1 μM) exhibited increased3[H]leucine incorporation by 120% and total TGF-β1 protein by 50% vs. culture in 5.5 mM d-glucose. Antisense ODN significantly decreased the high-glucose-stimulated TGF-β1 secretion and leucine incorporation. Continuous infusion for 10 days of ODN (100 μg/day) was achieved via osmotic minipumps in diabetic and nondiabetic mice. Sense ODN-treated streptozotocin-diabetic mice had 15.3% increase in kidney weight, 70% increase in α1(IV) collagen and 46% increase in fibronectin mRNA levels compared with nondiabetic mice. Treatment of diabetic mice with antisense ODN partially but significantly decreased kidney TGF-β1 protein levels and attenuated the increase in kidney weight and the α1(IV) collagen and fibronectin mRNAs. In conclusion, therapy with antisense TGF-β1 ODN decreases TGF-β1 production and attenuates high-glucose-induced proximal tubular cell hypertrophy in vitro and partially prevents the increase in kidney weight and extracellular matrix expression in diabetic mice.

scholarly journals Marine Alga Ecklonia cava Extract and Dieckol Attenuate Prostaglandin E2 Production in HaCaT Keratinocytes Exposed to Airborne Particulate Matter

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 190 ◽  
Author(s):  
Jae Won Ha ◽  
Hyerim Song ◽  
Seong Su Hong ◽  
Yong Chool Boo
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Particulate Matter ◽  
Prostaglandin E2 ◽  
Pge2 Production ◽  
Ecklonia Cava ◽  
Epidermal Keratinocytes ◽  
Hacat Keratinocytes ◽  
Cox 2 ◽  
Cox 1

Atmospheric particulate matter (PM) is an important cause of skin damage, and an increasing number of studies have been conducted to discover safe, natural materials that can alleviate the oxidative stress and inflammation caused by PM. It has been previously shown that the extract of Ecklonia cava Kjellman, a perennial brown macroalga, can alleviate oxidative stress in epidermal keratinocytes exposed to PM less than 10 microns in diameter (PM10). The present study was undertaken to further examine the anti-inflammatory effects of E. cava extract and its major polyphenolic constituent, dieckol. HaCaT keratinocytes were exposed to PM10 in the presence or absence of E. cava extract or dieckol and analyzed for their viability, prostaglandin E2 (PGE2) release, and gene expression of cyclooxygenase (COX)-1, COX-2, microsomal prostaglandin E2 synthase (mPGES)-1, mPGES-2, and cytosolic prostaglandin E2 synthase (cPGES). PM10 treatment decreased cell viability and increased the production of PGE2, and these changes were partially abrogated by E. cava extract. E. cava extract also attenuated the expression of COX-1, COX-2, and mPGES-2 stimulated by PM10. Dieckol attenuated PGE2 production and the gene expression of COX-1, COX-2, and mPGES-1 stimulated by PM10. This study demonstrates that E. cava extract and dieckol alleviate airborne PM10-induced PGE2 production in keratinocytes through the inhibition of gene expression of COX-1, COX-2, mPGES-1, and/or mPGES-2. Thus, E. cava extract and dieckol are potentially useful natural cosmetic ingredients for counteracting the pro-inflammatory effects of airborne PM.

scholarly journals Netrin-1 regulates the inflammatory response of neutrophils and macrophages, and suppresses ischemic acute kidney injury by inhibiting COX-2-mediated PGE2 production

2013 ◽  
Vol 83 (6) ◽  
pp. 1087-1098 ◽  
Author(s):  
Punithavathi V. Ranganathan ◽  
Calpurnia Jayakumar ◽  
Riyaz Mohamed ◽  
Zheng Dong ◽  
Ganesan Ramesh
Keyword(s):  
Acute Kidney Injury ◽  
Inflammatory Response ◽  
Kidney Injury ◽  
Pge2 Production ◽  
Ischemic Acute Kidney Injury ◽  
Cox 2
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