JAK-STAT and the renin-angiotensin system

Satou, Ryousuke; González-Villalobos, Romer A.

doi:10.4161/jkst.22729

Cited by 38 publications

(44 citation statements)

References 92 publications

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“…Enhanced interferon gamma (IFN-γ) formation in activated T cells, natural killer cells, and macrophages during the development of Ang II associated hypertension has also been demonstrated [Crowley et al , 2008, Saha et al , 2010]. In addition to the stimulating effect of IL-6 on proximal tubular AGT expression, IFN-γ increases AGT expression in PTC [Satou et al , 2012] as well as in hepatocytes [Jain et al , 2006]. These findings suggest that AGT synthesis in proximal tubules is stimulated via Ang II-induced pro-inflammatory factors, particularly IL-6 and IFN-γ, derived from immune cells, which may be primary mechanisms underlying elevated intrarenal AGT levels during Ang II-dependent hypertension.…”

Section: Introductionmentioning

confidence: 99%

Role of stimulated intrarenal angiotensinogen in hypertension

Satou

Shao

Navar

2015

Therapeutic Advances in Cardiovascular Disease

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Experimental models of hypertension and patients with inappropriately increased renin formation due to a stenotic kidney, arteriosclerotic narrowing of the renal arterioles or a rare juxtaglomerular cell tumor have shown a progressive augmentation of the intrarenal/intratubular renin-angiotensin system (RAS). The increased intrarenal angiotensin II (Ang II) elicits renal vasoconstriction and enhanced tubular sodium reabsorption in proximal and distal nephron segments. The enhanced intrarenal Ang II levels are due to both increased AT1 receptor mediated Ang II uptake and AT1 receptor dependent stimulation of renal angiotensinogen (AGT) mRNA and augmented AGT production. The increased AGT formation and secretion into the proximal tubular lumen leads to local formation of Ang II, which stimulates proximal transporters such as the sodium/hydrogen exchanger. Enhanced AGT production also leads to spillover of AGT into the distal nephron segments as reflected by AGT in the urine, which provides an index of intrarenal RAS activity. There is also increased Ang II concentration in distal nephron with stimulation of distal sodium transport. Increased urinary excretion of AGT has been demonstrated in patients with hypertension, Type 1 and Type 2 diabetes mellitus, and several types of chronic kidney diseases indicating an upregulation of intrarenal RAS activity.

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Section: Introductionmentioning

confidence: 99%

Role of stimulated intrarenal angiotensinogen in hypertension

Satou

Shao

Navar

2015

Therapeutic Advances in Cardiovascular Disease

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“…HTN in the INVEST participants. PTPRD codes for receptor-type protein tyrosine phosphatase receptor delta, which has been found to have roles in neuron growth and guidance as well as malignant glioma, although through its involvement in the STAT3 pathway could possibly play a role in intrarenal RAS signaling [65]. Further support for this is given by the identification of a SNP rs10739150 downstream of PTPRD that correlates with BP responsiveness in the African American group from this study (p=8.3 x 10 -6 ).…”

Section: Beta Blockersmentioning

confidence: 53%

Pharmacogenomics in Hypertension: Where We Stand Today

Cunningham¹,

Chapman²

2019

Preprint

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Hypertension is a common and growing medical problem that leads to enormous cardiovascular and kidney disease worldwide. While many drugs exist to treat hypertension, there is large individual variation in how a given individual responds to different agents, which contributes to dismal rates of hypertension control. While demographic factors predict which drugs may work better in certain individuals, a great degree of this variation has a genetic basis. In recent years, genome wide association studies have begun to identify specific gene variants that predict drug response to particular agents. This review identifies the major genetic variants influencing antihypertensive response that have emerged from this growing body of work. For novel genetic variants without a previously known biologic basis in blood pressure, it is crucial to validate initial findings in subsequent studies. This information may eventually lead to a more personalized approach to hypertension management that will improve blood pressure control and patient outcomes. The integration of this large amount of data and its real world application will be highly challenging, but strategies to accomplish this are discussed.

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“…PTPRD has been shown to be a tumor suppressor gene in malignant glioma and other human cancers and was found to dephosphorylate signal transducers and activators of transcription 3 (STAT3) [20]. There is increasing evidence that STAT3 is involved in regulation of BP and the intrarenal RAS through the JAK-STAT pathway [21]. SNPs in PTPRD gene have also been associated with diabetes [22,23] and plasma homocysteine levels [24].…”

Section: Discussionmentioning

confidence: 99%

PTPRD gene associated with blood pressure response to atenolol and resistant hypertension

Gong

McDonough

Beitelshees

et al. 2015

Journal of Hypertension

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Objective The aim of this study is to identify single-nucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the β-blocker atenolol. Methods Genome-wide association analysis of BP response to atenolol monotherapy was performed in 233 white participants with uncomplicated hypertension in the pharmacogenomic evaluation of antihypertensive responses study. Forty-two polymorphisms with P less than 10−5 for association with either diastolic or systolic response to atenolol monotherapy were validated in four independent groups of hypertensive individuals (total n = 2114). Results In whites, two polymorphisms near the gene PTPRD (rs12346562 and rs1104514) were associated with DBP response to atenolol (P = 3.2 × 10−6 and P = 5.9 × 10−6, respectively) with directionally opposite association for response to hydrochlorothiazide in another group of 228 whites (P = 0.0018 and P = 0.00012). A different polymorphism (rs10739150) near PTPRD was associated with response to atenolol in 150 black hypertensive individuals (P = 8.25 ×10−6). rs12346562 had a similar trend in association with response to bisoprolol (a different β-blocker) in 207 Finnish men in the genetics of drug responsiveness in essential hypertension study. In addition, an intronic single-nucleotide polymorphism (rs4742610) in the PTPRD gene was associated with resistant hypertension in whites and Hispanics in the international verapamil SR trandolapril study (meta-analysis P = 3.2 × 10−5). Conclusion PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.

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JAK-STAT and the renin-angiotensin system

Cited by 38 publications

References 92 publications

Role of stimulated intrarenal angiotensinogen in hypertension

Role of stimulated intrarenal angiotensinogen in hypertension

Pharmacogenomics in Hypertension: Where We Stand Today

PTPRD gene associated with blood pressure response to atenolol and resistant hypertension

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