Differential effects of two ROCK inhibitors, Fasudil and Y-27632, on optic nerve regeneration in adult cats

Ichikawa, Masahiro; Yoshida, Jun; Saito, Kiyoshi; Sagawa, Hiroe; Tokita, Yoshihito; Watanabe, Masami

doi:10.1016/j.brainres.2008.01.063

Cited by 35 publications

(21 citation statements)

References 74 publications

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“…Several signaling pathways drive liver regeneration (Huang et al , ; Natarajan et al , ), including the Hippo pathway (Loforese et al , ; Lu et al , ). The Hippo pathway is activated during liver regeneration (Grijalva et al , ) and primarily driven via the co‐transcriptional activator yes‐associated protein (YAP).…”

Section: Introductionmentioning

confidence: 99%

Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration

Meyer

Morales‐Navarrete

Seifert

et al. 2020

Molecular Systems Biology

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The mechanisms of organ size control remain poorly understood. A key question is how cells collectively sense the overall status of a tissue. We addressed this problem focusing on mouse liver regeneration. Using digital tissue reconstruction and quantitative image analysis, we found that the apical surface of hepatocytes forming the bile canalicular network expands concomitant with an increase in F‐actin and phospho‐myosin, to compensate an overload of bile acids. These changes are sensed by the Hippo transcriptional co‐activator YAP, which localizes to apical F‐actin‐rich regions and translocates to the nucleus in dependence of the integrity of the actin cytoskeleton. This mechanism tolerates moderate bile acid fluctuations under tissue homeostasis, but activates YAP in response to sustained bile acid overload. Using an integrated biophysical–biochemical model of bile pressure and Hippo signaling, we explained this behavior by the existence of a mechano‐sensory mechanism that activates YAP in a switch‐like manner. We propose that the apical surface of hepatocytes acts as a self‐regulatory mechano‐sensory system that responds to critical levels of bile acids as readout of tissue status.

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Section: Introductionmentioning

confidence: 99%

Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration

Meyer

Morales‐Navarrete

Seifert

et al. 2020

Molecular Systems Biology

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“…7–10 Additionally, ROCK inhibition regulates growth cone formation and axonal elongation after optic nerve injury. 11,12 However, to our knowledge the role of RhoA/ROCK in autonomic regulation of the penis has not been examined.…”

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confidence: 99%

Inhibition of Rho-Kinase Improves Erectile Function, Increases Nitric Oxide Signaling and Decreases Penile Apoptosis in a Rat Model of Cavernous Nerve Injury

Hannan¹,

Albersen

Kutlu³

et al. 2013

Journal of Urology

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Purpose Bilateral cavernous nerve injury results in up-regulation of ROCK signaling in the penis. This is linked to erectile dysfunction in an animal model of post-prostatectomy erectile dysfunction. We evaluated whether daily treatment with the ROCK inhibitor Y-27632 (Tocris Bioscience, Ellisville, Missouri) would prevent erectile dysfunction in a rat model of bilateral cavernous nerve injury. Materials and Methods Sprague-Dawley® rats underwent surgery to create sham (14) or bilateral (27) cavernous nerve injury. In the injury group 13 rats received treatment with Y-27632 (5 mg/kg twice daily) and 14 received vehicle. At 14 days after injury, rats underwent cavernous nerve stimulation to determine erectile function. Penes were assessed for neuronal and nitric oxide synthase membrane-endothelial nitric oxide synthase. ROCK2 was assessed by Western blot. Cyclic guanosine monophosphate was determined by enzyme-linked immunosorbent assay. Cavernous homogenates were tested for ROCK and protein kinase G enzymatic activity. Penile apoptosis was evaluated using the Apostain technique (Alexis, San Diego, California). Data were analyzed on ROCK using ANOVA and the t test. Results While erectile function was decreased in rats with bilateral cavernous nerve injury, daily administration of Y-27632 improved erectile responses. Injury decreased neuronal and nitric oxide synthase membrane-endothelial nitric oxide synthase but ROCK2 was significantly increased. Y-27632 treatment restored neuronal nitric oxide synthase, nitric oxide synthase membrane-endothelial nitric oxide synthase and cyclic guanosine monophosphate levels, and protein kinase G activity. Treatment significantly decreased ROCK2 protein and ROCK activity. There were significantly fewer apoptotic cells after treatment than in injured controls. Conclusions These results provide evidence for up-regulation of the RhoA/ROCK signaling pathway with detrimental effects on erectile function after bilateral cavernous nerve injury. ROCK inhibition improved erectile dysfunction associated with bilateral cavernous nerve injury by preserving penile nitric oxide bioavailability and decreasing penile apoptosis.

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“…This ROCK inhibitor induced an extension of the optic nerve axons beyond the crush site, whereas very few axons could pass through the crush site in the control group 69. In addition, knockdown of the RhoA gene by shRNA enhanced the regeneration of the damaged optic nerve in an animal model 70.…”

Section: Introductionmentioning

confidence: 93%

ROCK inhibitors for the treatment of ocular diseases

et al. 2017

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The Rho-kinase/ROCK (Rho-associated coiled-coil-containing protein kinase) pathway is involved in the pathogenesis of multiple ocular and systemic disorders. Recently, ROCK inhibitors have been suggested as novel treatments for various ocular diseases. Several in vitro, in vivo and clinical studies have demonstrated the safety and efficacy of ROCK inhibitors in the management of ocular disorders such as corneal epithelial and endothelial damage, glaucoma, retinal and choroidal neovascularisation, diabetic macular oedema and optic nerve disorders. In this review, these studies are explored with focus on the relevant clinical investigations.

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Differential effects of two ROCK inhibitors, Fasudil and Y-27632, on optic nerve regeneration in adult cats

Cited by 35 publications

References 74 publications

Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration

Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration

Inhibition of Rho-Kinase Improves Erectile Function, Increases Nitric Oxide Signaling and Decreases Penile Apoptosis in a Rat Model of Cavernous Nerve Injury

ROCK inhibitors for the treatment of ocular diseases

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