Rho-Associated Coiled-Coil Kinase (ROCK) in Molecular Regulation of Angiogenesis

Liu, Jing; Wada, Youichiro; Katsura, Mari; Tozawa, Hideto; Erwin, Nicholas A.; Kapron, Carolyn M.; Bao, Gang; Liu, Ju

doi:10.7150/thno.30305

Cited by 84 publications

(73 citation statements)

References 186 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, miR-136-3p was shown to repress the activation of EIF5A2 and the Rho A/ROCK signaling pathway. Multiple studies have established ROCK as a major downstream effector of the small GTP-binding protein Rho, and it is a significant mediator of angiogenesis and angiogenesis-related disorders [39,40]. EIF5A2 is a downstream target of Akt [41], and the ROCK signaling shared the activation status with the PI3K/Akt/ROCK pathway [42].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of microRNA-136-3p Alleviates Myocardial Injury in Coronary Artery Disease via the Rho A/ROCK Signaling Pathway

Lin

Dan

2020

Kidney Blood Press Res

View full text Add to dashboard Cite

KeywordsCoronary artery disease · MicroRNA-136-3p · Cardiac microvascular endothelial cells · EIF5A2 · Rho A/ROCK signaling pathway Abstract Objective: Coronary artery disease (CAD) is a cardiovascular disease that poses a fatal threat to human health, and the identification of potential biomarkers may help to delineate its pathophysiological mechanisms. Accumulating evidence has implicated microRNAs (miRNAs) in the pathogenesis and development of cardiovascular diseases. The present study aims to identify the expression of miRNA-136-3p (miR-136-3p) in CAD and further investigate its functional relevance in myocardial injury both in vitro and in vivo. Methods: Initially, CAD models were induced in rats by high-fat diet and intraperitoneal injection of pituitrin. Next, the effect of overexpressed miR-136-3p on cardiac function and pathological damage in myocardial tissue, cardiomyocyte apoptosis, oxidative stress and inflammatory response were assessed in CAD rats. Rat cardiac microvascular endothelial cells (CMECs) were isolated and cultured by the tissue explant method, and the CMEC injury model was induced by homocysteine (HCY). The function of miR-136-3p in vitro was further evaluated. Results: miR-136-3p was poorly expressed in the myocardial tissue of CAD rats and CMEC injury models. In vivo assays indicated that overexpressed miR-136-3p could improve cardiac function and alleviate pathological damage in myocardial tissue, accompanied by reduced oxidative stress and inflammatory response. Moreover, in vitro assays suggested that overexpression of miR-136-3p enhanced proliferation and migration while inhibiting apoptosis of HCY-stressed CMECs. Notably, we revealed that EIF5A2 was a target gene of miR-136-3p, and miR-136-3p inhibited EIF5A2 expression and activation of the Rho A/ROCK signaling pathway. Conclusion: In conclusion, the overexpression of miR-136-3p could potentially impede myocardial injury in vitro and in vivo in CAD through the blockade of the Rho A/ROCK signaling pathway, highlighting a potential miR-136-3p functional relevance in the treatment of CAD.

show abstract

Section: Discussionmentioning

confidence: 99%

Overexpression of microRNA-136-3p Alleviates Myocardial Injury in Coronary Artery Disease via the Rho A/ROCK Signaling Pathway

Lin

Dan

2020

Kidney Blood Press Res

View full text Add to dashboard Cite

show abstract

“…Therefore, dose‐dependent decrease in the expression of α‐SMA, CTGF, and PDGF was in line with the in vivo antifibrotic effects of these compounds, and also consistent with previous studies . Regarding the effect of the RhoA/ROCK pathway on the expression of CTGF, and PDGF, inhibition of this pathway can prevent the activation of HSCS, the expression of α‐SMA and the production of ECM. Atorvastatin has also been shown in a previous study to prevent the activation HSCs by controlling the RhoA/rho‐kinase pathway .…”

Section: Discussionmentioning

confidence: 85%

“…Accordingly, in various studies, the anti‐angiogenesis and antifibrotic effects of nilotinib and statin have been observed by the focus on the c‐Abl family, PDGF, PDGFR, c‐kit, and control of RhoA/ROCK, CTGF, and PDGF pathways . Therefore, to the importance of Bcr‐Abl activity and RhoA/ROCK, pathway, this study aimed to evaluate the antifibrotic potency of the combination of tyrosine kinase and rho‐kinase inhibitors.…”

Section: Discussionmentioning

confidence: 92%

“…In the activation process of HSCs, receptor and non‐receptor tyrosine kinase, including VEGFR, FGFR, PDGFR, c‐kit, c‐Abl, and Src, along with rho‐kinase, plays important roles. These receptors perform to control the activation of HSCs and intrahepatic angiogenesis by regulating the expression of transcriptional genes, such as CTGF, PDGF, and the α1 (1) and α2 (1) collagen …”

Section: Discussionmentioning

confidence: 99%

“…Atorvastatin has also been shown in a previous study to prevent the activation HSCs by controlling the RhoA/rho‐kinase pathway . Additionally, the importance of inhibition of the RhoA/rho‐kinase pathway in the regulation of PDGF has also been determined …”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Increasing the effectiveness of tyrosine kinase inhibitor (TKI) in combination with a statin in reducing liver fibrosis

Mohammadalipour

Hashemnia

Goudarzi

et al. 2019

Clin Exp Pharma Physio

View full text Add to dashboard Cite

It has been shown that both nilotinib as a tyrosine kinase inhibitor, and atorvastatin as a rho‐kinase inhibitor, have antifibrotic effects. Therefore, considering the relationship between these two pathways, this study aimed to investigate the effects of their co‐treatment against hepatic stellate cells (HSCs) activation and liver fibrosis. For this purpose, the activation of HSCs coincided with these therapies. Also, liver fibrosis by carbon tetrachloride (CCl4) was induced in male Wistar rats and treated simultaneously with these compounds. The expression of alpha‐smooth muscle actin (α‐SMA), connective tissue growth factor (CTGF), Ras homolog gene family, and member A (RhoA)/Rho‐associated protein kinase (ROCK) in HSCs were measured. The expression of transforming growth factor beta‐1 (TGF‐β1), its receptor (TβRII), CTGF, and platelets derived growth factor (PDGF), in the livers, were also investigated, all by real‐time PCR and western blot analysis. Also, histopathologic and immunohistochemical evaluations were performed to evaluate changes in liver fibrosis during treatment. The results indicated the down‐regulation of RhoA/ROCK, CTGF, and α‐SMA, and inhibition of the HSCs activation toward myofibroblasts. The results also showed that the combined use of atorvastatin and nilotinib has significantly higher inhibitory effects. The antifibrotic effects of atorvastatin and nilotinib co‐administration were also observed by histopathologic and immunohistochemical observations, and inhibiting the expression of TGF‐β1, TβRII, CTGF, and PDGF. Taken together, this study revealed that co‐administration of nilotinib–atorvastatin has novel antifibrotic effects, by inhibiting RhoA/ROCK, and CTGF pathway. Therefore, the importance of the common pathway of RhoA/ROCK and CTGF, in reducing fibrosis may almost be concluded.

show abstract

A Dual‐Antioxidative Coating on Transmucosal Component of Implant to Repair Connective Tissue Barrier for Treatment of Peri‐Implantitis

Li,

Tan,

Zheng

et al. 2023

Adv Healthcare Materials

View full text Add to dashboard Cite

Since the microgap between implant and surrounding connective tissue creates the pass for pathogen invasion, sustained pathological stimuli can accelerate macrophage‐mediated inflammation, therefore affecting peri‐implant tissue regeneration and aggravate peri‐implantitis. As the transmucosal component of implant, the abutment therefore needs to be biofunctionalized to repair the gingival barrier. Here, a mussel‐bioinspired implant abutment coating containing tannic acid (TA), cerium and minocycline (TA‐Ce‐Mino) is reported. TA provides pyrogallol and catechol groups to promote cell adherence. Besides, Ce3+/Ce4+ conversion exhibits enzyme‐mimetic activity to remove reactive oxygen species while generating O2, therefore promoting anti‐inflammatory M2 macrophage polarization to help create a regenerative environment. Minocycline is involved on the TA surface to create local drug storage for responsive antibiosis. Moreover, the underlying therapeutic mechanism is revealed whereby the coating exhibits exogenous antioxidation from the inherent properties of Ce and TA and endogenous antioxidation through mitochondrial homeostasis maintenance and antioxidases promotion. In addition, it stimulates integrin to activate PI3K/Akt and RhoA/ROCK pathways to enhance VEGF‐mediated angiogenesis and tissue regeneration. Combining the antibiosis and multidimensional orchestration, TA‐Ce‐Mino repairs soft tissue barriers and effector cell differentiation, thereby isolating the immune microenvironment from pathogen invasion. Consequently, this study provides critical insight into the design and biological mechanism of abutment surface modification to prevent peri‐implantitis.

show abstract

Rho-Associated Coiled-Coil Kinase (ROCK) in Molecular Regulation of Angiogenesis

Cited by 84 publications

References 186 publications

Overexpression of microRNA-136-3p Alleviates Myocardial Injury in Coronary Artery Disease via the Rho A/ROCK Signaling Pathway

Overexpression of microRNA-136-3p Alleviates Myocardial Injury in Coronary Artery Disease via the Rho A/ROCK Signaling Pathway

Increasing the effectiveness of tyrosine kinase inhibitor (TKI) in combination with a statin in reducing liver fibrosis

A Dual‐Antioxidative Coating on Transmucosal Component of Implant to Repair Connective Tissue Barrier for Treatment of Peri‐Implantitis

Contact Info

Product

Resources

About