Transforming growth factor β1 antagonizes the transcription, expression and vascular signaling of guanylyl cyclase/natriuretic peptide receptor A – role of δ<scp>EF</scp>1

Sen, Anagha; Kumar, Prerna; Garg, Renu; Lindsey, Sarah H.; Katakam, Prasad V. G.; Bloodworth, Meaghan; Pandey, Kailash N.

doi:10.1111/febs.13701

Cited by 8 publications

(10 citation statements)

References 67 publications

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“…First-strand cDNA was synthesized from 1 g total RNA in a final volume of 20 l reaction mixture using the RT 2 first strand kit (Roche, New York, NY). Quantitative real-time RT-PCR was done using the Mx3000P real-time-PCR system, as previously described (38,87). Data were analyzed using MxPro software (Stratagene, La Jolla, CA).…”

Section: Methodsmentioning

confidence: 99%

Genetic disruption ofNpr1depletes regulatory T cells and provokes high levels of proinflammatory cytokines and fibrosis in the kidneys of female mutant mice

Gogulamudi

Mani

Umadevi

et al. 2019

American Journal of Physiology-Renal Physiology

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The present study was designed to determine the effects of gene knockout of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) on immunogenic responses affecting kidney function and blood pressure (BP) in Npr1 (coding for GC-A/NPRA)-null mutant mice. We used female Npr1 gene-disrupted ( Npr1−/−, 0 copy), heterozygous ( Npr1+/−, 1 copy), wild-type ( Npr1+/+, 2 copy), and gene-duplicated ( Npr1++/++, 4 copy) mice. Expression levels of Toll-like receptor (TLR)2/TLR4 mRNA were increased 4- to 5-fold in 1-copy mice and 6- to 10-fold in 0-copy mice; protein levels were increased 2.5- to 3-fold in 1-copy mice and 4- to 5-fold in 0-copy mice. Expression of proinflammatory cytokines and BP was significantly elevated in 1-copy and 0-copy mice compared with 2-copy and 4-copy mice. In addition, 0-copy and 1-copy mice exhibited drastic reductions in regulatory T cells (Tregs). After rapamycin treatment, Tregs were increased by 17% ( P < 0.001) in 0-copy mice and 8% ( P < 0.001) in 1-copy mice. Renal mRNA and protein levels of TLR2 and TLR4 were decreased by 70% in 0-copy mice and 50% in 1-copy mice. There were significantly higher levels of Tregs and very low levels of TLR2/TLR4 expression in 4-copy mice ( P < 0.001). These findings indicate that the disruption of Npr1 in female mice triggers renal immunogenic pathways, which transactivate the expression of proinflammatory cytokines and renal fibrosis with elevated BP in mutant animals. The data suggest that rapamycin treatment attenuates proinflammatory cytokine expression, dramatically increases anti-inflammatory cytokines, and substantially reduces BP and renal fibrosis in mutant animals.

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Section: Methodsmentioning

confidence: 99%

Genetic disruption ofNpr1depletes regulatory T cells and provokes high levels of proinflammatory cytokines and fibrosis in the kidneys of female mutant mice

Gogulamudi

Mani

Umadevi

et al. 2019

American Journal of Physiology-Renal Physiology

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“…The male mice (C57/Bl6) were euthanized by deep anesthesia with isoflurane inhalation. Thoracic aorta was isolated and aortic rings were prepared using the previously described protocol with a minor modification 31,76 . Immediately after thoracotomy, the thoracic aorta was removed and placed in cold Dulbecco's PBS and cleaned by removing the surrounding fat and connective tissue.…”

Section: Scientific Reports |mentioning

confidence: 99%

“…After 6 h, another dose of ANG II was added, and incubation was continued. Vessels were mounted on a wire myograph and experiments were completed as previously described 31,81 . Vessels were preconstricted with prostaglandin F2α (PGF2α) and treated with increasing concentrations of ANP.…”

Section: Scientific Reports |mentioning

confidence: 99%

“…The NPRA has generally been considered to be the primary receptor of ANP and BNP, the reason being that most of the physiological effects of these hormones are triggered by rapidly activating this receptor and the generation of its intracellular second messenger cGMP 15,[18][19][20] . The recent studies have indicated that the ANP/NPRA system also has a central role in insulin resistance, obesity, and metabolic syndromes 11,21,22 .The expression and activation of NPRA is regulated by various hormonal agents, including angiotensin II (ANG II) 23-26 , endothelin 3,27 , and vasopressin 28 , as well as other stimuli such as osmoregulation 29,30 , autoregulation 19 , and cytokines and growth factors 29,31 . The pressure hormone ANG II exhibits the vascular constrictive effects and the retention of sodium and body fluid, thereby, increases the vascular tone and blood pressure 32,33 .…”

mentioning

confidence: 99%

“…The expression and activation of NPRA is regulated by various hormonal agents, including angiotensin II (ANG II) 23-26 , endothelin 3,27 , and vasopressin 28 , as well as other stimuli such as osmoregulation 29,30 , autoregulation 19 , and cytokines and growth factors 29,31 . The pressure hormone ANG II exhibits the vascular constrictive effects and the retention of sodium and body fluid, thereby, increases the vascular tone and blood pressure 32,33 .…”

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confidence: 99%

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Angiotensin II represses Npr1 expression and receptor function by recruitment of transcription factors CREB and HSF-4a and activation of HDACs

Arise

Kumar

Garg

et al. 2020

Sci Rep

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The two vasoactive hormones, angiotensin II (ANG II; vasoconstrictive) and atrial natriuretic peptide (ANP; vasodilatory) antagonize the biological actions of each other. ANP acting through natriuretic peptide receptor-A (NPRA) lowers blood pressure and blood volume. We tested hypothesis that ANG ii plays critical roles in the transcriptional repression of Npr1 (encoding NPRA) and receptor function. ANG II significantly decreased NPRA mRNA and protein levels and cGMP accumulation in cultured mesangial cells and attenuated Anp-mediated relaxation of aortic rings ex vivo. the transcription factors, cAMP-response element-binding protein (CREB) and heat-shock factor-4a (HSF-4a) facilitated the ANG II-mediated repressive effects on Npr1 transcription. Tyrosine kinase (TK) inhibitor, genistein and phosphatidylinositol 3-kinase (PI-3K) inhibitor, wortmannin reversed the ANG II-dependent repression of Npr1 transcription and receptor function. ANG II enhanced the activities of Class I histone deacetylases (HDACs 1/2), thereby decreased histone acetylation of H3K9/14ac and H4K8ac. The repressive effect of ANG II on Npr1 transcription and receptor signaling seems to be transduced by tK and PI-3K pathways and modulated by CREB, HSF-4a, HDACs, and modified histones. The current findings suggest that ANG II-mediated repressive mechanisms of Npr1 transcription and receptor function may provide new molecular targets for treatment and prevention of hypertension and cardiovascular diseases.Atrial and brain natriuretic peptides (ANP and BNP) are endogenous cardiac hormones that regulate sodium excretion, water balance, and steroidogenesis, processes that are all largely directed toward reducing blood pressure and blood volume 1-4 . Both ANP and BNP are primarily synthesized in atrial myocytes and to a much lesser extent, they are synthesized in ventricular cells and stored in dense granules 1,5 . A third peptide, C-type natriuretic peptide (CNP), which is highly homologous to ANP and BNP, is predominantly present in the endothelial cells and the central nervous system 6 . ANP and BNP exhibit their major effects in diverse organ systems, including kidneys, adrenal glands, heart, vasculature, gonads, and adipose tissues 2,7-12 . The early discovery of three related natriuretic peptides (NPs) hormones, prompted the cloning and characterization of three distinct subtypes of natriuretic peptide receptors (NPRs). These NP receptors included: natriuretic peptide receptor-A (NPRA), receptor-B (NPRB), and receptor-C (NPRC), with binding characteristics of ANP and BNP to NPRA, CNP to NPRB, and all three NPs (ANP, BNP, and CNP) to NPRC 13-17 . NPRA and NPRB, both of which contain a guanylyl cyclase (GC) domain, are also referred to, respectively, as GC-A/NPRA and GC-B/NPRB. The NPRA has generally been considered to be the primary receptor of ANP and BNP, the reason being that most of the physiological effects of these hormones are triggered by rapidly activating this receptor and the generation of its intracellular second messenger cGMP 15,[1...

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Synthesis of Novel Oxime and Benzofuran Chemical Frameworks Possessing Potent Anticholinesterase Activity: A SAR Study Related to Alzheimer Disease

et al. 2023

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Alzheimer Disease (AD) is a neurological disorder that causes the brain to shrink and brain cells to eventually die. Main symptom of AD is dementia. Today, approximately 50 million people worldwide are estimated to have AD. However, there is not a determined cure known against AD today. There are just four drugs against AD on the market. Unfortunately, none of them can totally destroy AD. Thus, discovering new molecules having capability to treat AD is required and significant. Benzofurans and oximes demonstrate a number of biological effects including anti‐inflammatory and brain‐barrier penetrating. For this reason, a number of novel compounds bearing oxime and benzofuran skeletons were designed and synthesized, and their anticholinesterase activities were investigated. Based on the results, several molecules demonstrated very strong anticholinesterase activities against both AChE and BChE enzymes, even much better than the reference drug molecule, Galantamine. Besides, structure‐activity relationship (SAR) studies belonging to these chemical cores were revealed through this study for the first time. Various derivatives with different types of selective activities were obtained, which brightens the detailed SAR tendency of these molecules. This study can contribute to discover a novel lead drug molecule against AD, which is an urgent need.

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Transforming growth factor β1 antagonizes the transcription, expression and vascular signaling of guanylyl cyclase/natriuretic peptide receptor A – role of δEF1

Cited by 8 publications

References 67 publications

Genetic disruption ofNpr1depletes regulatory T cells and provokes high levels of proinflammatory cytokines and fibrosis in the kidneys of female mutant mice

Genetic disruption ofNpr1depletes regulatory T cells and provokes high levels of proinflammatory cytokines and fibrosis in the kidneys of female mutant mice

Angiotensin II represses Npr1 expression and receptor function by recruitment of transcription factors CREB and HSF-4a and activation of HDACs

Synthesis of Novel Oxime and Benzofuran Chemical Frameworks Possessing Potent Anticholinesterase Activity: A SAR Study Related to Alzheimer Disease

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