Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

Adebiyi, Adebowale; Soni, Hitesh; John, Theresa A.; Yang, Fen

doi:10.1016/j.yexcr.2014.03.011

Cited by 22 publications

(26 citation statements)

References 76 publications

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“…In vitro studies have shown that caveolin-1, a membrane lipid raft marker, co-immunoprecipitates with AT 1 R upon agonist stimulation and these rafts play a critical role for AT 1 R-mediated signal transduction. 33,34 Altogether, it is conceivable that upon RAS over-activation, AT 1a R could move to a closer location, from which its downstream signals can affect ADAM17 in a more efficient way.…”

Section: Discussionmentioning

confidence: 99%

Clinical Relevance and Role of Neuronal AT ₁ Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension

Sriramula

Xia

et al. 2017

Circulation Research

159

166

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Rationale Neurogenic hypertension is characterized by an increase in sympathetic activity and often resistance to drug treatments. We previously reported that it is also associated with a reduction of Angiotensin Converting Enzyme 2 (ACE2) and an increase in A Disintegrin And Metalloprotease 17 (ADAM17) activity in experimental hypertension. In addition, while multiple cells within the central nervous system have been involved in the development of neurogenic hypertension, the contribution of ADAM17 has not been investigated. Objective To assess the clinical relevance of this ADAM17-mediated ACE2 shedding in hypertensive patients and further identify the cell types and signaling pathways involved in this process. Methods and Results Using a mass spectrometry-based assay, we identified ACE2 as the main enzyme converting Ang II into Ang-(1–7) in human cerebrospinal fluid (CSF). We also observed an increase in ACE2 activity in the CSF of hypertensive patients, which was correlated with systolic blood pressure. Moreover, the increased level of tumor necrosis factor (TNF)-α in those CSF samples confirmed that ADAM17 was up-regulated in the hypertensive patients’ brain. To further assess the interaction between brain renin-angiotensin system and ADAM17, we generated mice lacking Angiotensin II type 1 receptors (AT1R) specifically on neurons. Our data reveal that despite expression on astrocytes and other cells types in the brain, ADAM17 up-regulation during DOCA-salt hypertension occurs selectively on neurons and neuronal AT1R are indispensable to this process. Mechanistically, reactive oxygen species (ROS) and extracellular signal-regulated kinase (ERK) were found to mediate ADAM17 activation. Conclusions Our data demonstrate that AT1R promote ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a loss in compensatory activity during neurogenic hypertension.

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Section: Discussionmentioning

confidence: 99%

Clinical Relevance and Role of Neuronal AT ₁ Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension

Sriramula

Xia

et al. 2017

Circulation Research

159

166

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“…However, we do not exclude that in podocytes in diabetic condition the expression of other members of TRPC channels family could be altered as well. Furthermore, members of the TRPC family are shown to be expressed in mesangial cells 41 42 43 , and it was reported that Ang II signaling plays an important role in this type of cells 44 45 . Interestingly, Graham et al demonstrated that abundance of TRPC6 is decreased in cultured mesangial cells treated with high glucose 46 47 .…”

Section: Discussionmentioning

confidence: 99%

“…Ang II released into the renal interstitium is one of the key mediators of renal inflammation and fibrosis in progressive chronic nephropathies. High intrarenal Ang II levels have been definitively linked to glomeruli damage in DN 2 43 44 45 46 , whereas the fundamental effector of Ang II in the podocytes remained to be determined. TRPC channels have been associated with Ang II-induced calcium influx in many renal cell types 17 18 19 20 21 .…”

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confidence: 99%

Podocyte injury in diabetic nephropathy: implications of angiotensin II – dependent activation of TRPC channels

Ilatovskaya

Levchenko

Lowing

et al. 2015

Sci Rep

103

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Injury to podocytes is considered a major contributor to diabetic kidney disease: their loss causes proteinuria and progressive glomerulosclerosis. Podocyte depletion may result from improper calcium handling due to abnormal activation of the calcium permeant TRPC (Transient Receptor Potential Canonical) channels. Angiotensin II (Ang II) levels are found to be elevated in diabetes; furthermore, it was reported that Ang II causes activation of TRPC6 in podocytes. We hypothesized here that Ang II-mediated calcium influx is aggravated in the podocytes under the conditions of type 1 diabetic nephropathy (DN). Diabetes was induced in the Dahl Salt-Sensitive rats by an injection of streptozotocin (STZ-SS). Eleven weeks post treatment was sufficient for the animals to develop hyperglycemia, excessive urination, weight loss, microalbuminuria, nephrinuria and display renal histological lesions typical for patients with DN. Patch-clamp electrophysiology performed on podocytes of the freshly isolated glomeruli showed enhanced basal TRPC channel activity in the STZ-SS rats, and increased response to Ang II; total calcium influx triggered by Ang II application was also augmented in podocytes of these rats. Our studies have a strong potential for advancing the understanding of TRPC-mediated effects on podocytopenia in DN initiation.

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“…Renal glomeruli were isolated from the pigs (<1-week-old) by serial sieving of renal cortical homogenates using sterile stainless steel meshes. GMCs were then cultured from decapsulated glomeruli as we have previously described 58 .…”

Section: Methodsmentioning

confidence: 99%

“…Cultured GMCs were homogenized in ice-cold RIPA buffer supplemented with a protease inhibitor cocktail (Thermo Scientific, Rockford, IL). Following isolation, proteins were separated and detected as we have previously described 58 59 .…”

Section: Methodsmentioning

confidence: 99%

TRPC6 channel activation promotes neonatal glomerular mesangial cell apoptosis via calcineurin/NFAT and FasL/Fas signaling pathways

Soni

Adebiyi

2016

Sci Rep

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Glomerular mesangial cell (GMC) proliferation and death are involved in the pathogenesis of glomerular disorders. The mechanisms that control GMC survival are poorly understood, but may include signal transduction pathways that are modulated by changes in intracellular Ca2+ ([Ca2+]i) concentration. In this study, we investigated whether activation of the canonical transient receptor potential (TRPC) 6 channels and successive [Ca2+]i elevation alter neonatal GMC survival. Hyperforin (HF)-induced TRPC6 channel activation increased [Ca2+]i concentration, inhibited proliferation, and triggered apoptotic cell death in primary neonatal pig GMCs. HF-induced neonatal GMC apoptosis was not associated with oxidative stress. However, HF-induced TRPC6 channel activation stimulated nuclear translocation of the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). HF also increased cell death surface receptor Fas ligand (FasL) level and caspase-8 activity in the cells; effects mitigated by [Ca2+]i chelator BAPTA, calcineurin/NFAT inhibitor VIVIT, and TRPC6 channel knockdown. Accordingly, HF-induced neonatal GMC apoptosis was attenuated by BAPTA, VIVIT, Fas blocking antibody, and a caspase-3/7 inhibitor. These findings suggest that TRPC6 channel-dependent [Ca2+]i elevation and the ensuing induction of the calcineurin/NFAT, FasL/Fas, and caspase signaling cascades promote neonatal pig GMC apoptosis.

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Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

Cited by 22 publications

References 76 publications

Clinical Relevance and Role of Neuronal AT ₁ Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension

Clinical Relevance and Role of Neuronal AT ₁ Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension

Podocyte injury in diabetic nephropathy: implications of angiotensin II – dependent activation of TRPC channels

TRPC6 channel activation promotes neonatal glomerular mesangial cell apoptosis via calcineurin/NFAT and FasL/Fas signaling pathways

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Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

Cited by 22 publications

References 76 publications

Clinical Relevance and Role of Neuronal AT 1 Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension

Clinical Relevance and Role of Neuronal AT 1 Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension

Podocyte injury in diabetic nephropathy: implications of angiotensin II – dependent activation of TRPC channels

TRPC6 channel activation promotes neonatal glomerular mesangial cell apoptosis via calcineurin/NFAT and FasL/Fas signaling pathways

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Clinical Relevance and Role of Neuronal AT ₁ Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension

Clinical Relevance and Role of Neuronal AT ₁ Receptors in ADAM17-Mediated ACE2 Shedding in Neurogenic Hypertension