Involvement of Rho-associated coiled-coil kinase signaling inhibition in TGF-β1/Smad2, 3 signal transduction in vitro

Feng, Zhaohui; Zhang, Xiaohui; Zhao, Jiaqi; Ma, Junze

doi:10.18240/ijo.2017.12.03

Cited by 3 publications

(3 citation statements)

References 33 publications

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“…Transforming growth factor-b is the most potent inducer of myofibroblast differentiation and acts by activating the canonical Smad pathway or the non-Smad pathways, including Rho/ROCK signaling and different branches of the MAPK pathway (16,43). The ROCK inhibitors were reported to inhibit TGF-b-induced myofibroblast differentiation by regulating the Smad or MAPK signaling pathways (19,44). For example, Y-27632 suppressed TGF-b-induced phosphorylation of Smad3, but not that of Smad2, in ocular Tenon's capsule fibroblasts (44).…”

Section: Discussionmentioning

confidence: 99%

“…The ROCK inhibitors were reported to inhibit TGF-b-induced myofibroblast differentiation by regulating the Smad or MAPK signaling pathways (19,44). For example, Y-27632 suppressed TGF-b-induced phosphorylation of Smad3, but not that of Smad2, in ocular Tenon's capsule fibroblasts (44). It also inhibited TGF-b-induced phosphorylation of ERK and JNK, but not that of p38, in renal mesangial cells (19).…”

Section: Discussionmentioning

confidence: 99%

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Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves’ Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways

et al. 2021

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Transforming growth factor-β (TGF-β)-induced differentiation of orbital fibroblasts into myofibroblasts is an important pathogenesis of Graves’ ophthalmopathy (GO) and leads to orbital tissue fibrosis. In the present study, we explored the antifibrotic effects of simvastatin and ROCK inhibitor Y-27632 in primary cultured GO orbital fibroblasts and tried to explain the molecular mechanisms behind these effects. Both simvastatin and Y-27632 inhibited TGF-β-induced α-smooth muscle actin (α-SMA) expression, which serves as a marker of fibrosis. The inhibitory effect of simvastatin on TGF-β-induced RhoA, ROCK1, and α-SMA expression could be reversed by geranylgeranyl pyrophosphate, an intermediate in the biosynthesis of cholesterol. This suggested that the mechanism of simvastatin-mediated antifibrotic effects may involve RhoA/ROCK signaling. Furthermore, simvastatin and Y-27632 suppressed TGF-β-induced phosphorylation of ERK and p38. The TGF-β-mediated α-SMA expression was suppressed by pharmacological inhibitors of p38 and ERK. These results suggested that simvastatin inhibits TGF-β-induced myofibroblast differentiation via suppression of the RhoA/ROCK/ERK and p38 MAPK signaling pathways. Thus, our study provides evidence that simvastatin and ROCK inhibitors may be potential therapeutic drugs for the prevention and treatment of orbital fibrosis in GO.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves’ Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways

et al. 2021

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“…Rho-associated protein kinases (ROCKs) are involved in a variety of cellular activities, which include cell adhesion, proliferation, metabolism, apoptosis and cell cycle regulation (12). Y-27632 is a selective ROCK inhibitor, which can be used to inhibit the Rho signalling pathway (13). In the current study, Y-27632 was added to the culture medium to enhance the proliferation of functional in vitro -cultured rabbit CECs (RCECs).…”

Section: Introductionmentioning

confidence: 99%

Ex�vivo construction of rabbit corneal endothelial cell sheets on a porcine descemet membrane graft

et al. 2019

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The aim of the present study was to investigate the feasibility of a new graft construction method using rabbit corneal endothelial cells (RCECs) and a porcine descemet membrane (DM) carrier. RCECs were isolated and the experimental group was treated with Y-27632, whereas the control group were cultured in medium without Y-27632. RCEC morphology was observed using an inverted microscope, and cell proliferation and apoptosis were detected by flow cytometry. To confirm the presence of RCECs, reverse transcription-quantitative PCR was used to detect gene expression levels of Na+-K+-ATPase, aquaporin 1, collagen α 2 (IV), collagen α 1 (VIII) and keratin-12. Histocompatibility testing was used to detect porcine DM antigenicity. A DM-RCEC graft was constructed, and morphology was observed using alizarin red-trypan blue and haematoxylin and eosin staining. Cell membrane potential was measured to evaluate the physical function of the DM-RCEC graft. Complex graft tension was measured using a modified tension detector and compared with fresh porcine DM-endothelium complex. In vitro -cultured RCECs formed a monolayer with a polygon morphology and cobblestone-like arrangement. In vitro -cultured RCECs exhibited typical RCEC characteristics before and after transplantation. The proliferation rates of the experimental and control groups were 62.68 and 34.50%, respectively (P<0.05); the apoptosis rates of the experimental and control groups were 8.99 and 35.68%, respectively (P<0.05). There was no antigenicity observed with the porcine DM. The action potential amplitude of the experimental and control groups was over −80 mV, reflecting normal RCEC physiological function. The tension measurements of the experimental and control groups were 20.0248±1.048 and 20.5013±0.657 g, respectively (P>0.05). Taken together, the results of the present study demonstrated that Y-27632 enhanced RCEC proliferation. In addition, the findings revealed the successful ex vivo construction of a RCEC sheet on a porcine DM graft.

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The Expression and Role of Hypoxia-induced Factor-1α in Human Tenon’s Capsule Fibroblasts under Hypoxia

Qin

Chen

et al. 2020

Current Eye Research

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Involvement of Rho-associated coiled-coil kinase signaling inhibition in TGF-β1/Smad2, 3 signal transduction in vitro

Abstract: The inhibition of ROCK signaling may be a potential therapeutic candidate for the treatment of the filtration channel fibrosis.

Cited by 3 publications

References 33 publications

Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves’ Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways

Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves’ Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways

Ex�vivo construction of rabbit corneal endothelial cell sheets on a porcine descemet membrane graft

The Expression and Role of Hypoxia-induced Factor-1α in Human Tenon’s Capsule Fibroblasts under Hypoxia

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