scholarly journals Activation of the prostaglandin E 2 EP 2 receptor attenuates renal fibrosis in unilateral ureteral obstructed mice and human kidney slices

2019 ◽  
Vol 227 (1) ◽  
Author(s):  
Michael Schou Jensen ◽  
Henricus A. M. Mutsaers ◽  
Stine Julie Tingskov ◽  
Michael Christensen ◽  
Mia Gebauer Madsen ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Human Kidney ◽  
Prostaglandin E ◽  
Kidney Slices

scholarly journals Tamoxifen attenuates renal fibrosis in human kidney slices and rats subjected to unilateral ureteral obstruction

2021 ◽  
Vol 133 ◽  
pp. 111003
Author(s):  
Stine Julie Tingskov ◽  
Michael Schou Jensen ◽  
Casper-Emil Tingskov Pedersen ◽  
Isabela Bastos Binotti Abreu de Araujo ◽  
Henricus A.M. Mutsaers ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Human Kidney ◽  
Unilateral Ureteral Obstruction ◽  
Kidney Slices

Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis

2016 ◽  
Vol 170 ◽  
pp. 8-16.e1 ◽  
Author(s):  
Elisabeth G.D. Stribos ◽  
Theerut Luangmonkong ◽  
Anna M. Leliveld ◽  
Igle J. de Jong ◽  
Willem J. van Son ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Human Kidney ◽  
Kidney Slices

Characterization of the Uptake of Organic Anion Transporter (OAT) 1 and OAT3 Substrates by Human Kidney Slices

2007 ◽  
Vol 321 (1) ◽  
pp. 362-369 ◽  
Author(s):  
Yoshitane Nozaki ◽  
Hiroyuki Kusuhara ◽  
Tsunenori Kondo ◽  
Maki Hasegawa ◽  
Yoshiyuki Shiroyanagi ◽  
...  
Keyword(s):  
Organic Anion ◽  
Human Kidney ◽  
Organic Anion Transporter ◽  
Kidney Slices ◽  
Anion Transporter

Renal fibrosis in precision-cut kidney slices

2016 ◽  
Vol 790 ◽  
pp. 57-61 ◽  
Author(s):  
Elisabeth G.D. Stribos ◽  
Jan-Luuk Hillebrands ◽  
Peter Olinga ◽  
Henricus A.M. Mutsaers
Keyword(s):  
Renal Fibrosis ◽  
Kidney Slices

scholarly journals Dopamine DA2-receptor activation inhibits noradrenaline release in human kidney slices

1993 ◽  
Vol 43 (1) ◽  
pp. 197-204 ◽  
Author(s):  
Lars C. Rump ◽  
Eckhard Schwertfeger ◽  
Martin J. Schuster ◽  
Ulrike Schaible ◽  
Alexander Frankenschmidt ◽  
...  
Keyword(s):  
Noradrenaline Release ◽  
Human Kidney ◽  
Receptor Activation ◽  
Kidney Slices ◽  
Da2 Receptor

The effect of tamoxifen on gender differences in unilateral ureteral obstructed rats and human kidney slices

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Stine Julie Tingskov ◽  
Michael Schou Jensen ◽  
Rikke Nørregaard
Keyword(s):  
Gender Differences ◽  
Human Kidney ◽  
Kidney Slices

ADAM17 upregulation in human renal disease: a role in modulating TGF-α availability?

2009 ◽  
Vol 297 (3) ◽  
pp. F781-F790 ◽  
Author(s):  
W. B. Melenhorst ◽  
L. Visser ◽  
A. Timmer ◽  
M. C. van den Heuvel ◽  
C. A. Stegeman ◽  
...  
Keyword(s):  
Renal Function ◽  
Growth Factor ◽  
Renal Disease ◽  
Renal Fibrosis ◽  
Cellular Proliferation ◽  
Human Kidney ◽  
Macrophage Infiltration ◽  
Peritubular Capillaries ◽  
Egfr Ligand ◽  
Proximal Tubular

A disintegrin and metalloproteinase (ADAM)17 sheds growth factors from the cell membrane, including epidermal growth factor receptor (EGFR) ligand transforming growth factor (TGF)-α. In mice, angiotensin II infusion induces renal fibrosis via ADAM17-mediated TGF-α shedding and subsequent EGFR activation. Pharmacological ADAM17 inhibition reduced renal fibrotic lesions and improved renal function, positioning ADAM17 as a promising target of intervention in renal disease. We studied ADAM17 expression in the human kidney. ADAM17 mRNA was constitutively expressed in normal adult kidneys, with highest expression in distal tubules. In human renal disease, ADAM17 was de novo expressed in proximal tubules, peritubular capillaries, and glomerular mesangium and upregulated in podocytes. Glomerular mesangial and endothelial ADAM17 were associated with mesangial matrix expansion, focal glomerulosclerosis, and glomerular macrophage infiltration ( P < 0.01). Peritubular capillary and proximal tubular ADAM17 were associated with interstitial fibrosis and interstitial macrophage infiltration ( P < 0.05). Both glomerular and interstitial ADAM17 were associated with decreased renal function ( P < 0.05). In renal fibrosis, ADAM17 colocalized with TGF-α. Moreover, in cultured human podocytes and proximal tubular cells, pharmacological ADAM17 inhibition reduced constitutive TGF-α shedding by 78% ( P < 0.005) and 100% ( P < 0.05), respectively, and phorbol ester-induced TGF-α shedding by 84% ( P < 0.005) and 92% ( P = 0.005), respectively. Finally, ADAM17 inhibition reduced cellular proliferation. In conclusion, the ADAM17 expression pattern and its role in shedding TGF-α from cultured human kidney cells suggest a role in the development of fibrosis. Since EGFR signaling is implicated in renal fibrosis, targeting ADAM17 to reduce availability of EGFR ligand TGF-α may represent a promising way of intervention in human renal disease.

scholarly journals Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targetingex vivo

2015 ◽  
Vol 8 (10) ◽  
pp. 1227-1236 ◽  
Author(s):  
Fariba Poosti ◽  
Bao Tung Pham ◽  
Dorenda Oosterhuis ◽  
Klaas Poelstra ◽  
Harry van Goor ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Kidney Slices ◽  
Study Development

scholarly journals Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction

2017 ◽  
Vol 312 (1) ◽  
pp. F121-F133 ◽  
Author(s):  
Renfei Luo ◽  
Yutaka Kakizoe ◽  
Feifei Wang ◽  
Xiang Fan ◽  
Shan Hu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Collecting Duct ◽  
Unilateral Ureteral Obstruction ◽  
Prostaglandin E ◽  
Expression Levels ◽  
Collagen Iii ◽  
Tgf Β1

Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 to prostaglandin E2 (PGE2), plays an important role in a variety of inflammatory diseases. We investigated the contribution of mPGES-1 to renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) for 7 days using wild-type (WT) and mPGES-1 knockout (KO) mice. UUO induced increased mRNA and protein expression of mPGES-1 and cyclooxygenase-2 in WT mice. UUO was associated with increased renal PGE2 content and upregulated PGE2 receptor (EP) 4 expression in obstructed kidneys of both WT and mPGES-1 KO mice; EP4 expression levels were higher in KO mice with UUO than those in WT mice. Protein expression of NLRP3 inflammasome components ASC and interleukin-1β was significantly increased in obstructed kidneys of KO mice compared with that in WT mice. mRNA expression levels of fibronectin, collagen III, and transforming growth factor-β1 (TGF-β1) were significantly higher in obstructed kidneys of KO mice than that in WT mice. In KO mice, protein expression of fibronectin and collagen III was markedly increased in obstructed kidneys compared with WT mice, which was associated with increased phosphorylation of protein kinase B (AKT). EP4 agonist CAY10598 attenuated increased expression of collagen I and fibronectin induced by TGF-β1 in inner medullary collecting duct 3 cells. Moreover, CAY10598 prevented the activation of NLRP3 inflammasomes induced by angiotensin II in human proximal tubule cells (HK2). In conclusion, these findings suggested that mPGES-1 exerts a potentially protective effect against renal fibrosis and inflammation induced by UUO in mice.

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