Advances in the studies of roles of Rho/Rho-kinase in diseases and the development of its inhibitors

Guan, Ronggui; Xu, Xiaoyu; Chen, Meihui; Hu, Haiyan; Hu, Ge; Wen, Shulin; Zhou, Shiying; Pi, Rongbiao

doi:10.1016/j.ejmech.2013.10.048

Cited by 73 publications

(49 citation statements)

References 68 publications

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“…For instance, ROCK inhibitors have been shown to be effective to mitigate a large number of fibrotic diseases 46 including reperfusion injury in the liver, 47 cardiovascular diseases, 48,49 tissue fibrosis, 50 cerebral ischemia, 51 peritoneal fibrosis, 28 amyotrophic lateral sclerosis, 52 and pulmonary hypertension. 53,54 Fasudil is a specific ROCK inhibitor 55 and is the first kinase inhibitor drug used in a clinical setting in Japan.…”

Section: Discussionmentioning

confidence: 99%

Leiomyoma Cells in 3-Dimensional Cultures Demonstrate an Attenuated Response to Fasudil, a Rho-Kinase Inhibitor, When Compared to 2-Dimensional Cultures

et al. 2014

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Uterine leiomyomata are common benign tumors in women of reproductive age and demonstrate an attenuated response to mechanical signaling that involves Rho and integrins. To further characterize the impairment in Rho signaling, we studied the effect of Rho-kinase inhibitor, fasudil, on extracellular matrix production, in 2-dimensional (2D) and 3-dimensional (3D) cultures of leiomyoma and myometrial cells. Leiomyoma 2D cultures demonstrated a rapid decrease in gene transcripts and protein for fibronectin, procollagen 1A, and versican. In 3D cultures, fibronectin and procollagen 1A proteins demonstrated increased levels at lower concentrations of fasudil, followed by a concentration-dependent decrease. Versican protein increased up to 3-fold, whereas fibromodulin demonstrated a significant decrease of 1.92-fold. Myometrial 2D or 3D cultures demonstrated a decrease in all proteins after 72 hours of treatment. The 3D leiomyoma cultures demonstrated a significant increase in active RhoA, followed by a concentration-dependent decrease at higher concentrations. A concentration-dependent increase in phosphoextracellular regulated signal kinase and proapoptotic protein Bax was observed in 3D leiomyoma cultures. Fasudil relaxed the contraction of the 3D collagen gels caused by myometrium and leiomyoma cell growth. These findings indicate that the altered state of Rho signaling in leiomyoma was more clearly observed in 3D cultures. The results also suggest that fasudil may have clinical applicability for treatment of uterine leiomyoma.

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Section: Discussionmentioning

confidence: 99%

Leiomyoma Cells in 3-Dimensional Cultures Demonstrate an Attenuated Response to Fasudil, a Rho-Kinase Inhibitor, When Compared to 2-Dimensional Cultures

et al. 2014

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“…Given the different roles of ROCK1 and ROCK2 highlighted in the past few years, an additional challenge is to discover isoform-specific ROCK inhibitors. Active research has thus been carried out recently to develop a new series of ROCK inhibitors based on different scaffolds (Guan et al, 2013;Pan et al, 2013;Feng and LoGrasso, 2014). Here, we summarize typical examples of these new compounds.…”

Section: A Rho-associated Kinase Inhibitorsmentioning

confidence: 99%

Rho Kinases in Health and Disease: From Basic Science to Translational Research

Loirand¹

2015

Pharmacol Rev

167

133

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“…The impairment of RhoA results in the loss of its expression and activity that may play a role in the development of DGC [78]. RhoA, a member of the Rho family, is a small GTPase protein that plays a fundamental role in regulating diverse cellular processes, such as cell growth, cell survival, polarity, adhesion, cell migration, and differentiation [79,80,81,82]. The studies have shown that genetic alterations in the RhoA pathway, including recurrent RHOA mutations and RhoGAP fusion along with the CDH1 mutations, are quite common in DGC but not in other variants of gastric cancer [36,76].…”

Section: Factors Associated With Molecular Pathogenicity Of Dgcmentioning

confidence: 99%

Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity

Ansari

Gantuya

Tuan

et al. 2018

IJMS

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Gastric cancer is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide. Incidence and mortality differ depending on the geographical region and gastric cancer ranks first in East Asian countries. Although genetic factors, gastric environment, and Helicobacter pylori infection have been associated with the pathogenicity and development of intestinal-type gastric cancer that follows the Correa’s cascade, the pathogenicity of diffuse-type gastric cancer remains mostly unknown and undefined. However, genetic abnormalities in the cell adherence factors, such as E-cadherin and cellular activities that cause impaired cell integrity and physiology, have been documented as contributing factors. In recent years, H. pylori infection has been also associated with the development of diffuse-type gastric cancer. Therefore, in this report, we discuss the host factors as well as the bacterial factors that have been reported as associated factors contributing to the development of diffuse-type gastric cancer.

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Advances in the studies of roles of Rho/Rho-kinase in diseases and the development of its inhibitors

Cited by 73 publications

References 68 publications

Leiomyoma Cells in 3-Dimensional Cultures Demonstrate an Attenuated Response to Fasudil, a Rho-Kinase Inhibitor, When Compared to 2-Dimensional Cultures

Leiomyoma Cells in 3-Dimensional Cultures Demonstrate an Attenuated Response to Fasudil, a Rho-Kinase Inhibitor, When Compared to 2-Dimensional Cultures

Rho Kinases in Health and Disease: From Basic Science to Translational Research

Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity

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