<i>β</i>-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats

Cuevas, Catherina A.; Tapia-Rojas, Cheril; Céspedes, Carlos L.; Inestrosa, Nibaldo C.; Vio, Carlos P.

doi:10.1155/2015/726012

Cited by 20 publications

(16 citation statements)

References 43 publications

(56 reference statements)

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“…Masson's staining showed that the renal fibrosis was significantly elevated in 2K1C rats compared with Sham rats, which was consistent with previous findings ( 33 – 35 ). Intraperitoneally administrated with high dose of vaccarin or captopril abrogated the fibrosis in the right kidney in 2K1C rats ( Fig.…”

Section: Resultssupporting

confidence: 92%

Vaccarin alleviates hypertension and nephropathy in renovascular hypertensive rats

et al. 2017

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The kidney is an important organ in the regulation of blood pressure, and it is also one of the primary target organs of hypertension. Kidney damage in response to hypertension eventually leads to renal insufficiency. The authors previously demonstrated that vaccarin exhibits a protective role in endothelial injury. However, the effects of vaccarin on the two-kidney, one clip (2K1C) renovascular hypertension model and subsequent kidney injury have yet to be fully elucidated. The present study was designed to investigate the roles and mechanisms of vaccarin in attenuating hypertension and whether vaccarin had beneficial effects on kidney injury. The 2K1C rats had greater fibrosis, apoptosis, reactive oxygen species production, inflammation, angiotensin II (Ang II) and angiotensin type 1 (AT1) receptors in the right kidney compared with normotensive rats, which were alleviated by a high dose of vaccarin and captopril. Vaccarin treatment attenuated hypertension, reduced fibrosis markers, NADPH oxidase (NOX)-2, NOX-4, 3-nitrotyrosine, tumor necrosis factor-α, interleukin 1β (IL-1β), and IL-6 protein levels and altered pro-apoptotic protein levels including caspase-3, anti-apoptosis protein B cell lymphoma (Bcl)-2 and Bcl-2 associated X, apoptosis regulator in the right kidney of 2K1C rats. These findings suggest that the protective effects of vaccarin on the right kidney in renovascular hypertension are possibly due to downregulation of fibrosis, inflammatory molecules, oxidative stress, Ang II, and AT1 receptor levels.

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Section: Resultssupporting

confidence: 92%

Vaccarin alleviates hypertension and nephropathy in renovascular hypertensive rats

et al. 2017

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“…In addition, in the mouse collecting duct cell line M1, ANG II induces ␤-catenin protein, fibronectin mRNA, and collagen I mRNA, which are attenuated with ␤-catenin destabilization reagent pyrvinium pamoate (192). Moreover, pyrvinium pamoate treatment ameliorates kidney induction of ␤-catenin, collagen I, fibronectin, and osteopontin in a rat model of renovascular hypertension, suggesting the role of the Wnt/␤-catenin pathway in ANG II-dependent renal fibrosis (193). It is also interesting to note that multiple RAS genes are targets of the Wnt/␤-catenin pathway.…”

Section: Wnt/␤-catenin Pathwaymentioning

confidence: 94%

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

778

780

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The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (ATR) is believed to mediate most functions of ANG II in the system. ATR utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between ATR signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. ATR remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.

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“…AngII enhances Wnt1 expression, β-catenin nuclear translocation in mouse podocytes, with inhibition of Wnt/β-catenin pathway attenuating podocyte injury (139). β-catenin destabilization reagent also inhibits AngII-induced β-catenin, collagen I, fibronectin and osteopontin in mouse collecting duct cell or kidney of renovascular hypertensive rat (140, 141). Thus, there is accumulating evidence indicating a close relationship between the Wnt/β-catenin pathway and AT1 receptor in regard to cardiovascular remodeling and chronic kidney diseases.…”

Section: Cascades Of Wnt Notch Hippo and Mitochondriamentioning

confidence: 99%

AT1 receptor signaling pathways in the cardiovascular system

Kawai

Forrester

O’Brien

et al. 2017

Pharmacological Research

174

126

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The importance of the renin angiotensin aldosterone system in cardiovascular physiology and pathophysiology has been well described whereas the detailed molecular mechanisms remain elusive. The angiotensin II type 1 receptor (AT1 receptor) is one of the key players in the renin angiotensin aldosterone system. The AT1 receptor promotes various intracellular signaling pathways resulting in hypertension, endothelial dysfunction, vascular remodeling and end organ damage. Accumulating evidence shows the complex picture of AT1 receptor-mediated signaling; AT1 receptor-mediated heterotrimeric G protein-dependent signaling, transactivation of growth factor receptors, NADPH oxidase and ROS signaling, G protein-independent signaling, including the β-arrestin signals and interaction with several AT1 receptor interacting proteins. In addition, there is functional cross-talk between the AT1 receptor signaling pathway and other signaling pathways. In this review, we will summarize an up to date overview of essential AT1 receptor signaling events and their functional significances in the cardiovascular system.

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β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats

Cited by 20 publications

References 43 publications

Vaccarin alleviates hypertension and nephropathy in renovascular hypertensive rats

Vaccarin alleviates hypertension and nephropathy in renovascular hypertensive rats

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

AT1 receptor signaling pathways in the cardiovascular system

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