Fasudil inhibits ER stress-induced VCAM-1 expression by modulating unfolded protein response in endothelial cells

Kawanami, Daiji; Matoba, Keiichiro; Okada, Ryosuke; Tsukamoto, Masami; Koyama, Jun; Ishizawa, Shin; Kanazawa, Yasushi; Yokota, Tamotsu; Utsunomiya, Kazunori

doi:10.1016/j.bbrc.2013.04.091

Cited by 15 publications

(12 citation statements)

References 27 publications

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“…Of significance, 4-PBA reduced Rho kinase activity, while fasudil decreased BiP expression, indicating crosstalk between ER stress and Rho kinase in the context of increased Notch3 activity in CADASIL. Interactions between these pathways have been reported in other systems, as evidenced by (i) reduction in renal Notch signaling in response to Rho kinase inhibition (52), (ii) Notch3-induced activation of Rho kinase in pluripotent stem cells (51), (iii) decreased vascular Rho A signaling in Notch3-deficient mice (33), (iv) amelioration of ER stress by Rho kinase inhibitors (30), and (v) Notch3 association with ER stress (32).…”

Section: Discussionmentioning

confidence: 94%

“…AMFR6, EDEM1, and FBXO6 participate in protein degradation, while MBTPS1, VIMP, and SYVN1 play a role in protein removal (46). Associated with ER stress in CADASIL VSMCs was upregulation of Rho kinase, which itself has been shown to influence ER stress (30). RhoA/Rho kinase signaling influences VSMC contraction, growth, and cytoskeletal organization and is an important regulator of Ca 2+ -independent vasocontraction and endothelium-independent vasorelaxation, processes that were impaired in CADASIL VSMCs.…”

Section: Discussionmentioning

confidence: 99%

“…A relationship between ER stress and Rho kinase has been demonstrated in VSMCs (30) and experimental models of vascular damage, where the ER stress response promotes activation of Rho kinase (30,31). These phenomena may be regulated by Notch3-dependent processes because Notch3 associates with the protein-folding chaperone binding immunoglobulin protein (BiP; also known as GRP78) in the ER (32), mutations in Notch3 cause formation and retention of aggregates in the ER (23), and Notch3 modulates vascular RhoA/Rho kinase signaling (33).…”

Section: Introductionmentioning

confidence: 99%

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ER stress and Rho kinase activation underlie the vasculopathy of CADASIL

et al. 2019

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ER stress and Rho kinase activation underlie the vasculopathy of CADASIL

et al. 2019

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“…ROCK blockade also restores normal motor nerve conduction velocity in diabetic rats by mediating proper localization of adhesion-related molecules in myelinating Schwann cells [40]. Another study in endothelial cells demonstrated that ROCK acts as a key player in vascular inflammation [41].…”

Section: Rock Signalingmentioning

confidence: 95%

Targeting Redox Imbalance as an Approach for Diabetic Kidney Disease

et al. 2020

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Diabetic kidney disease (DKD) is a worldwide public health problem. It is the leading cause of end-stage renal disease and is associated with increased mortality from cardiovascular complications. The tight interactions between redox imbalance and the development of DKD are becoming increasingly evident. Numerous cascades, including the polyol and hexosamine pathways have been implicated in the oxidative stress of diabetes patients. However, the precise molecular mechanism by which oxidative stress affects the progression of DKD remains to be elucidated. Given the limited therapeutic options for DKD, it is essential to understand how oxidants and antioxidants are controlled in diabetes and how oxidative stress impacts the progression of renal damage. This review aims to provide an overview of the current status of knowledge regarding the pathological roles of oxidative stress in DKD. Finally, we summarize recent therapeutic approaches to preventing DKD with a focus on the anti-oxidative effects of newly developed anti-hyperglycemic agents.

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“…Our group identified ROCK as an essential regulator of the proliferation of VSMCs induced by PDGF-BB (38) . With respect to endothelial cells, Kawanami et al showed that ROCK inhibition attenuates the vascular cellular adhesion molecule 1 (VCAM1) expression induced by tunicamycin, an inducer of endoplasmic reticulum (ER) stress (56) . Mechanistically, activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), which are involved in ER stress-induced cellular apoptosis, are downregulated by the ROCK inhibition.…”

Section: Rock In Other Diabetic Vascular Complicationsmentioning

confidence: 99%

ROCK Inhibition May Stop Diabetic Kidney Disease

Matoba

Takeda

Nagai

et al. 2020

JMA J

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Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and is strongly associated with cardiovascular mortality. Given the pandemic of obesity and diabetes, the elucidation of the molecular underpinnings of DKD and establishment of effective therapy are urgently required. Studies over the past decade have identified the activated renin-angiotensin system (RAS) and hemodynamic changes as important therapeutic targets. However, given the residual risk observed in patients treated with RAS inhibitors and/or sodium glucose co-transporter 2 inhibitors, the involvement of other molecular machinery is likely, and the elucidation of such pathways represents fertile ground for the development of novel strategies. Rho-kinase (ROCK) is a serine/threonine kinase that is under the control of small GTPase protein Rho. Many fundamental cellular processes, including migration, proliferation, and survival are orchestrated by ROCK through a mechanism involving cytoskeletal reorganization. From a pathological standpoint, several analyses provide compelling evidence supporting the hypothesis that ROCK is an important regulator of DKD that is highly pertinent to cardiovascular disease. In cell-based studies, ROCK is activated in response to a diverse array of external stimuli associated with diabetes, and renal ROCK activity is elevated in the context of type 1 and 2 diabetes. Experimental studies have demonstrated the efficacy of pharmacological or genetic inhibition of ROCK in the prevention of diabetes-related histological and functional abnormalities in the kidney. Through a bird’s eye view of ROCK in renal biology, the present review provides a conceptual framework that may be widely applicable to the pathological processes of multiple organs and illustrate novel therapeutic promise in diabetology.

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Fasudil inhibits ER stress-induced VCAM-1 expression by modulating unfolded protein response in endothelial cells

Cited by 15 publications

References 27 publications

ER stress and Rho kinase activation underlie the vasculopathy of CADASIL

ER stress and Rho kinase activation underlie the vasculopathy of CADASIL

Targeting Redox Imbalance as an Approach for Diabetic Kidney Disease

ROCK Inhibition May Stop Diabetic Kidney Disease

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