Pharmacological inhibition of protease-activated receptor-2 reduces crescent formation in rat nephrotoxic serum nephritis

Clinical and Experimental Pharmacology & Physiology
Yingjie HanD J Nikolic-Paterson

Abstract

Glomerular crescent formation is a hallmark of rapidly progressive forms of glomerulonephritis. Thrombosis and macrophage infiltration are features of crescent formation in human and experimental kidney disease. Protease-activated receptor-2 (PAR-2) is a G-protein coupled receptor that links coagulation and inflammation. This study investigated whether pharmacological inhibition of PAR-2 can suppress glomerular crescent formation in rat nephrotoxic serum nephritis (NTN). Disease was induced in Wistar Kyoto rats by immunisation with sheep IgG followed by administration of sheep nephrotoxic serum. Rats (n = 8/group) received the PAR-2 antagonist (GB88, 10 mg/kg/p.o.), vehicle or no treatment starting 3 days before nephrotoxic serum injection and continuing until day 14. Vehicle and untreated rats developed thrombosis and macrophage infiltration in the glomerular tuft and Bowman's space in conjunction with prominent crescent formation. Activation of JNK signalling and proliferation in parietal epithelial cells was associated with crescent formation. GB88 treatment significantly reduced crescent formation with a substantial reduction in glomerular thrombosis, reduced macrophage infiltration in Bowman's space, and reduced activation...Continue Reading

References

Sep 1, 1978·The American Journal of Medicine·P A MorrinH Kreis
Jan 1, 1995·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·H Y LanR C Atkins
Feb 7, 1998·Kidney International·H Y LanR C Atkins
Jan 19, 2005·Journal of Pharmacological Sciences·Toru KankeAtsufumi Kawabata
Jun 29, 2007·Kidney International·R S FlancD J Nikolic-Paterson
Jul 21, 2007·The American Journal of Pathology·Leon MoussaPeter G Tipping
Aug 19, 2007·American Journal of Physiology. Renal Physiology·David A VeseyDavid W Johnson
Sep 25, 2007·The Journal of Pathology·M H De BorstH van Goor
Nov 10, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Agneta SiegbahnTeet Velling
Jan 18, 2008·Journal of the American Society of Nephrology : JASN·Paul S ThornerSusan Quaggin
Feb 4, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·Frank Y MaDavid J Nikolic-Paterson
Nov 18, 2009·Journal of the American Society of Nephrology : JASN·Bart SmeetsMarcus J Moeller
Dec 5, 2009·Journal of the American Society of Nephrology : JASN·Jennifer SmithFrederick W K Tam
Jul 10, 2010·Journal of the American Society of Nephrology : JASN·Annelies E BerdenIngeborg M Bajema
Apr 8, 2011·American Journal of Respiratory and Critical Care Medicine·Malgorzata WygreckaPhilipp Markart
Apr 27, 2011·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yingjie HanDavid J Nikolic-Paterson
Oct 6, 2011·Seminars in Immunopathology·Andrea S Rothmeier, Wolfram Ruf
Oct 27, 2011·The Journal of Pharmacology and Experimental Therapeutics·Rink-Jan LohmanDavid P Fairlie
Jan 28, 2012·Journal of the American Society of Nephrology : JASN·Eva-Maria SickingMarcus J Moeller
Apr 3, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rink-Jan LohmanDavid P Fairlie
Jan 4, 2013·American Journal of Physiology. Renal Physiology·David A VeseyDavid P Fairlie
Aug 22, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Junxian LimDavid P Fairlie
May 14, 2014·British Journal of Pharmacology·J Y SuenD P Fairlie
Dec 21, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·J Y SuenD P Fairlie
Nov 9, 2017·Frontiers in Physiology·Keren GrynbergDavid J Nikolic-Paterson

❮ Previous
Next ❯

Citations

Jul 25, 2021·International Journal of Molecular Sciences·Tyrone L R HumphriesDavid A Vesey

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.