A current overview of RhoA, RhoB, and RhoC functions in vascular biology and pathology

Eckenstaler, Robert; Hauke, Michael; Benndorf, Ralf A.

doi:10.1016/j.bcp.2022.115321

Cited by 23 publications

(10 citation statements)

References 425 publications

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“…RHOB deficiency inhibited pathological angiogenesis in ischemic retina patients, implying that RHOB alleviates symptoms by promoting the formation of lymphatic vessels following injury or in the presence of inflammation ( 57 ). Interestingly, RHOB also activates IL-1β (interleukin 1β), LPS (lipopolysaccharide), and TNFα (tumor necrosis factor α) in an inflammatory setting ( 54 ), contrary to previous observations. However, its mechanism of action in OA is unclear and remains to be investigated.…”

Section: Discussioncontrasting

confidence: 95%

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Identification of immune-associated genes in diagnosing osteoarthritis with metabolic syndrome by integrated bioinformatics analysis and machine learning

Wang

et al. 2023

Front. Immunol.

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BackgroundIn the pathogenesis of osteoarthritis (OA) and metabolic syndrome (MetS), the immune system plays a particularly important role. The purpose of this study was to find key diagnostic candidate genes in OA patients who also had metabolic syndrome.MethodsWe searched the Gene Expression Omnibus (GEO) database for three OA and one MetS dataset. Limma, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms were used to identify and analyze the immune genes associated with OA and MetS. They were evaluated using nomograms and receiver operating characteristic (ROC) curves, and finally, immune cells dysregulated in OA were investigated using immune infiltration analysis.ResultsAfter Limma analysis, the integrated OA dataset yielded 2263 DEGs, and the MetS dataset yielded the most relevant module containing 691 genes after WGCNA, with a total of 82 intersections between the two. The immune-related genes were mostly enriched in the enrichment analysis, and the immune infiltration analysis revealed an imbalance in multiple immune cells. Further machine learning screening yielded eight core genes that were evaluated by nomogram and diagnostic value and found to have a high diagnostic value (area under the curve from 0.82 to 0.96).ConclusionEight immune-related core genes were identified (FZD7, IRAK3, KDELR3, PHC2, RHOB, RNF170, SOX13, and ZKSCAN4), and a nomogram for the diagnosis of OA and MetS was established. This research could lead to the identification of potential peripheral blood diagnostic candidate genes for MetS patients who also suffer from OA.

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Section: Discussioncontrasting

confidence: 95%

“…RHOB is a Rho GTPase with a C-terminus and an N-terminus, the latter of which contains a G domain, also known as the RhoA-like domain ( 54 ). Because chromosome 2 retains RHOB ’s genetic information and lacks the alternative RHOB precursor mRNA, only one RHOB protein sequence can be translated ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of immune-associated genes in diagnosing osteoarthritis with metabolic syndrome by integrated bioinformatics analysis and machine learning

Wang

et al. 2023

Front. Immunol.

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“…The role of the Rho family of small GTPases as key regulators of angiogenesis has been well established, and it also plays an essential role in transmitting signals downstream of VEGF [ 41 , 61 , 62 ]. Specifically, Rho proteins appear to be direct downstream targets of VEGF-mediated endothelial cell signaling, leading to activation of RhoA, Rac1, and Cdc42 within several minutes after VEGF stimulation [ 36 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Y-27632 Impairs Angiogenesis on Extra-Embryonic Vasculature in Post-Gastrulation Chick Embryos

Duess

Gosemann

Gheorghescu

et al. 2023

Toxics

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Y-27632 inhibits Rho-associated coiled-coil-containing protein kinase (ROCK) signaling, which is involved in various embryonic developmental processes, including angiogenesis, by controlling actin cytoskeleton assembly and cell contractility. Administration of Y-27632 impairs cytoskeletal arrangements in post-gastrulation chick embryos, leading to ventral body wall defects (VBWDs). Impaired angiogenesis has been hypothesized to contribute to VBWDs. ROCK is essential in transmitting signals downstream of vascular endothelial growth factor (VEGF). VEGF-mediated angiogenesis induces gene expressions and alterations of the actin cytoskeleton upon binding to VEGF receptors (VEGFRs). The aim of this study was to investigate effects of Y-27632 on angiogenesis in post-gastrulation chick embryos during early embryogenesis. After 60 h incubation, embryos in shell-less culture were treated with Y-27632 or vehicle for controls. Y-27632-treated embryos showed reduced extra-embryonic blood vessel formation with impaired circulation of the yolk sac, confirmed by fractal analysis. Western blot confirmed impaired ROCK downstream signaling by decreased expression of phosphorylated myosin light chain. Interestingly, RT-PCR demonstrated increased gene expression of VEGF and VEGFR-2 1 h post-treatment. Protein levels of VEGF were higher in Y-27632-treated embryos at 8 h following treatment, whereas no difference was seen in membranes. We hypothesize that administration of Y-27632 impairs vessel formation during angiogenesis, which may contribute to failure of VWB closure, causing VBWDs.

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“…The Rho family is an integral part of the Ras superfamily of small-molecule guanosine triphosphatases (GTPases), comprising RhoA, RhoB, and RhoC [ 33 ]. RhoA plays a pivotal role in regulating myosin contractility; RhoB regulates cytokine transport and cell proliferation; and RhoC plays a crucial role in cell motility [ 34 - 36 ]. Dysregulation of the Rho protein family plays a key role in the development of various human diseases.…”

Section: Rho/rock Pathwaymentioning

confidence: 99%

Rho Kinase (ROCK) Inhibitors for the Treatment of Glaucoma

Wu,

Wei,

Chen

et al. 2024

CDT

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Glaucoma is the most common cause of irreversible blindness worldwide. It is characterized by progressive optic nerve degeneration and loss of visual field. Pathological increased intraocular pressure is its main modifiable risk factor. Rho kinase inhibitors are developed as a new class of glaucoma medication that increases outflow facility from the conventional aqueous humor outflow pathway. Additionally, they also have neuropective and anti-scarring effects that can might increase the success rate of glaucoma filtration surgery. This review aims to summarize the current concept of Rho kinase inhibitor in the treatment of glaucoma from beach to bedside.

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A current overview of RhoA, RhoB, and RhoC functions in vascular biology and pathology

Cited by 23 publications

References 425 publications

Identification of immune-associated genes in diagnosing osteoarthritis with metabolic syndrome by integrated bioinformatics analysis and machine learning

Identification of immune-associated genes in diagnosing osteoarthritis with metabolic syndrome by integrated bioinformatics analysis and machine learning

Y-27632 Impairs Angiogenesis on Extra-Embryonic Vasculature in Post-Gastrulation Chick Embryos

Rho Kinase (ROCK) Inhibitors for the Treatment of Glaucoma

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