scholarly journals Protease-activated receptors in kidney disease progression

2016 ◽  
Vol 311 (6) ◽  
pp. F1140-F1144 ◽  
Author(s):  
Oleg Palygin ◽  
Daria V. Ilatovskaya ◽  
Alexander Staruschenko
Keyword(s):  
Disease Progression ◽  
Serine Proteases ◽  
Mesangial Cells ◽  
Protease Activated Receptors ◽  
Renal Disease Progression ◽  
Protease Cleavage ◽  
Tethered Ligand ◽  
Kidney Disease Progression ◽  
Inflammatory Regulation ◽  
Functional Mechanisms

Protease-activated receptors (PARs) are members of a well-known family of transmembrane G protein-coupled receptors (GPCRs). Four PARs have been identified to date, of which PAR1 and PAR2 are the most abundant receptors, and have been shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligand that can be unmasked by serine protease cleavage. The receptors are activated by endogenous serine proteases, such as thrombin (acts on PARs 1, 3, and 4) and trypsin (PAR2). PARs can be involved in glomerular, microvascular, and inflammatory regulation of renal function in both normal and pathological conditions. As an example, it was shown that human glomerular epithelial and mesangial cells express PARs, and these receptors are involved in the pathogenesis of crescentic glomerulonephritis, glomerular fibrin deposition, and macrophage infiltration. Activation of these receptors in the kidney also modulates renal hemodynamics and glomerular filtration rate. Clinical studies further demonstrated that the concentration of urinary thrombin is associated with glomerulonephritis and type 2 diabetic nephropathy; thus, molecular and functional mechanisms of PARs activation can be directly involved in renal disease progression. We briefly discuss here the recent literature related to activation of PAR signaling in glomeruli and the kidney in general and provide some examples of PAR1 signaling in glomeruli podocytes.

scholarly journals Protease Activated Receptors and Arthritis

2021 ◽  
Vol 22 (17) ◽  
pp. 9352
Author(s):  
Flora Lucena ◽  
Jason J. McDougall
Keyword(s):  
Serine Proteases ◽  
Vascular Reactivity ◽  
Structural Integrity ◽  
Therapeutic Potential ◽  
G Protein Coupled Receptors ◽  
Tissue Remodelling ◽  
Protease Activated Receptors ◽  
Tethered Ligand ◽  
Arthritic Joints ◽  
G Protein Coupled

The catabolic and destructive activity of serine proteases in arthritic joints is well known; however, these enzymes can also signal pain and inflammation in joints. For example, thrombin, trypsin, tryptase, and neutrophil elastase cleave the extracellular N-terminus of a family of G protein-coupled receptors and the remaining tethered ligand sequence then binds to the same receptor to initiate a series of molecular signalling processes. These protease activated receptors (PARs) pervade multiple tissues and cells throughout joints where they have the potential to regulate joint homeostasis. Overall, joint PARs contribute to pain, inflammation, and structural integrity by altering vascular reactivity, nociceptor sensitivity, and tissue remodelling. This review highlights the therapeutic potential of targeting PARs to alleviate the pain and destructive nature of elevated proteases in various arthritic conditions.

scholarly journals Protease-Activated Receptors: Contribution to Physiology and Disease

2004 ◽  
Vol 84 (2) ◽  
pp. 579-621 ◽  
Author(s):  
VALERIA S. OSSOVSKAYA ◽  
NIGEL W. BUNNETT
Keyword(s):  
Protease Inhibitors ◽  
Serine Proteases ◽  
Inflammatory Cells ◽  
Coagulation Factors ◽  
Control Mechanisms ◽  
Physiological Control ◽  
Protease Activated Receptors ◽  
Future Challenges ◽  
Tethered Ligand ◽  
Selective Agonists

Ossovskaya, Valeria S., and Nigel W. Bunnett. Protease-Activated Receptors: Contribution to Physiology and Disease. Physiol Rev 84: 579–621, 2004; 10.1152/physrev.00028.2003.—Proteases acting at the surface of cells generate and destroy receptor agonists and activate and inactivate receptors, thereby making a vitally important contribution to signal transduction. Certain serine proteases that derive from the circulation (e.g., coagulation factors), inflammatory cells (e.g., mast cell and neutrophil proteases), and from multiple other sources (e.g., epithelial cells, neurons, bacteria, fungi) can cleave protease-activated receptors (PARs), a family of four G protein-coupled receptors. Cleavage within the extracellular amino terminus exposes a tethered ligand domain, which binds to and activates the receptors to initiate multiple signaling cascades. Despite this irreversible mechanism of activation, signaling by PARs is efficiently terminated by receptor desensitization (receptor phosphorylation and uncoupling from G proteins) and downregulation (receptor degradation by cell-surface and lysosomal proteases). Protease signaling in tissues depends on the generation and release of proteases, availability of cofactors, presence of protease inhibitors, and activation and inactivation of PARs. Many proteases that activate PARs are produced during tissue damage, and PARs make important contributions to tissue responses to injury, including hemostasis, repair, cell survival, inflammation, and pain. Drugs that mimic or interfere with these processes are attractive therapies: selective agonists of PARs may facilitatehealing, repair, and protection, whereas protease inhibitors and PAR antagonists can impede exacerbated inflammation and pain. Major future challenges will be to understand the role of proteases and PARs in physiological control mechanisms and human diseases and to develop selective agonists and antagonists that can be used to probe function and treat disease.

scholarly journals P0741CHRONIC KIDNEY DISEASE PROGRESSION IN A LARGE PREVENTION COHORT IN COLOMBIA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Angela Rivera ◽  
Angelito Bernardo ◽  
Jasmin Vesga ◽  
Izcay Ronderos ◽  
Mauricio Sanabria
Keyword(s):  
Kidney Disease ◽  
Disease Progression ◽  
Prevention Program ◽  
Reduction Rate ◽  
Progression Rate ◽  
Ckd Progression ◽  
Care Services ◽  
Kaplan Meier ◽  
Observational Cohort ◽  
Kidney Disease Progression

Abstract Background and Aims Chronic kidney disease (CKD) is a syndrome that today has important implications for the health of populations and the economic sustainability of health systems around the world, therefore strategies to slow disease progression are necessary. Aims: To estimate the incidence of renal replacement therapy (RRT) in a cohort of patients included in a CKD secondary prevention program and to describe the decrease of the estimated glomerular filtration rate (eGFR). Method This is a historical, multicenter, observational cohort study in a prevention program between January 1, 2010, and December 31, 2017, with follow-up until December 31, 2018, at the Renal Care Services (RCS) network. Socio-demographic and clinical characteristics of all patients were summarized descriptively. We estimated the incidence of RRT rate with Kaplan Meier analysis. Progression rate to RRT was analyzed by mixed-effects model adjusted for the eGFR reduction rate at 180 days; the model considered the diagnosis of diabetes. Results 7131 patients met the inclusion criteria for data analysis. The mean age was 65 years, 50.5% were female, (Table 1). There were 577 events of RRT with a rate of 2.02 events of RRT per 100 patients-year [95% CI,1.86 to 2.19], characteristics at the RRT initiation are presented in Table 2. At the beginning of the program the eGFR was 45.3 ml / min / 1.73m2 in non-diabetics, and 40.9 3 ml / min / 1.73m2 in diabetics. The CKD progression was - 0.48 ml / min / 1.73m2 per 180 days in diabetics and - 0.20 ml / min / 1.73m2 per 180 days in non-diabetics. The final events of the cohort are presented in Figure 1; the mortality rate was 0.89 events per 100 patients-year [95% CI, 0,79 to 1,01]. Conclusion This population of patients in a CKD prevention program presented a low rate of initiation of dialysis therapy and a slight decrease of eGFR; the diabetic status influences the CKD progression.

scholarly journals The Severity of Diabetic Retinopathy Is an Independent Factor for the Progression of Diabetic Nephropathy

2020 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Shi-Chue Hsing ◽  
Chia-Cheng Lee ◽  
Chin Lin ◽  
Jiann-Torng Chen ◽  
Yi-Hao Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Renal Disease ◽  
Disease Progression ◽  
Renal Disease Progression ◽  
Hazard Ratios ◽  
Stage Renal Disease ◽  
End Stage

(1) Background: It has rarely been studied whether the severity of diabetic retinopathy (DR) could influence renal disease progression in end-stage renal disease (ESRD) and chronic kidney disease (CKD) in patients with type 2 diabetes. The aim of this study was to evaluate renal disease progression in ESRD and CKD according to DR severity in patients with type 2 diabetes. (2) Methods: We included 1329 patients and divided the cohort into two end-points. The first was to trace the incidence of ESRD in all enrolled participants and the other was to follow their progression to CKD. (3) Results: Significantly higher crude hazard ratios (HRs) of ESRD incidence in all enrolled participants were noted, and this ratio increased in a stepwise fashion. However, after adjustment, DR severity was not associated with ESRD events. Therefore, a subgroup of 841 patients without CKD was enrolled to track their progression to CKD. Compared with no diabetic retinopathy, the progression of CKD increased in a stepwise fashion, from mild nonproliferative diabetic retinopathy (NPDR) to moderate NPDR, to severe NPDR and to proliferative diabetic retinopathy (PDR), both in the crude and adjusted models. (4) Conclusions: The severity of retinopathy appeared to be associated with renal lesions and the development of CKD. Our findings suggest that the severity of DR is a risk factor for progression to CKD. Therefore, diabetic retinopathy is useful for prognosticating the clinical course of diabetic kidney disease.

scholarly journals Effectiveness of integrated care on delaying chronic kidney disease progression in rural communities of Thailand ( ESCORT ‐2) trials

Nephrology ◽  
2021 ◽  
Author(s):  
Teerawat Thanachayanont ◽  
Methee Chanpitakkul ◽  
Jukkapong Hengtrakulvenit ◽  
Podjanee Watcharakanon ◽  
Watcharapong Wisansak ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Rural Communities ◽  
Kidney Disease ◽  
Disease Progression ◽  
Integrated Care ◽  
Chronic Kidney Disease Progression ◽  
Kidney Disease Progression
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