Up‐regulation of Rac1 in the bronchial smooth muscle of murine experimental asthma

Kai, Yudai; Motegi, Momoko; Suzuki, Yuta; Takeuchi, Hiroto; Harada, Yui; Sato, Fumiaki; Chiba, Yoshihiko; Kamei, Junzo; Sakai, Hiroyasu

doi:10.1111/bcpt.13204

Cited by 10 publications

(8 citation statements)

References 26 publications

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“…The growth inhibition of BC cells induced by EHT1864 is related to the dual inhibition of PI3K-AKT-mTORC1 and MEK-ERK pathways (179). Studies have shown that Rac1 plays an important role in the contraction of various smooth muscles, such as bronchial smooth muscle, bladder smooth muscle, and prostate smooth muscle (180)(181)(182)(183). Although both EHT1864 and NSC23766 are Rac1 inhibitors, they have different pharmacological mechanisms in the inhibition of different smooth muscles (182,184,185), and EHT1864 tends to perform better (186,187).…”

Section: General Rac1 Inhibitormentioning

confidence: 99%

Rac1, A Potential Target for Tumor Therapy

et al. 2021

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RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

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Section: General Rac1 Inhibitormentioning

confidence: 99%

Rac1, A Potential Target for Tumor Therapy

et al. 2021

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“…2015; Kai et al . 2019 a , b ). Carbachol induced phosphorylation of both PAK T423 and β‐catenin S675 , but not β‐catenin S552 in C2C12 myotubes (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…2015; Kai et al . 2019 a , b ). This suggests the β‐catenin S675 phosphorylation may be sufficient to regulate glucose transport.…”

Section: Discussionmentioning

confidence: 99%

β‐Catenin is required for optimal exercise‐ and contraction‐stimulated skeletal muscle glucose uptake

Masson

Woodhead

D’Souza

et al. 2021

The Journal of Physiology

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Key points Loss of β‐catenin impairs in vivo and isolated muscle exercise/contraction‐stimulated glucose uptake. β‐Catenin is required for exercise‐induced skeletal muscle actin cytoskeleton remodelling. β‐Catenin675 phosphorylation during exercise may be intensity dependent. Abstract The conserved structural protein β‐catenin is an emerging regulator of vesicle trafficking in multiple tissues and supports insulin‐stimulated glucose transporter 4 (GLUT4) translocation in skeletal muscle by facilitating cortical actin remodelling. Actin remodelling may be a convergence point between insulin and exercise/contraction‐stimulated glucose uptake. Here we investigated whether β‐catenin is involved in regulating exercise/contraction‐stimulated glucose uptake. We report that the muscle‐specific deletion of β‐catenin induced in adult mice (BCAT‐mKO) impairs both exercise‐ and contraction (isolated muscle)‐induced glucose uptake without affecting running performance or canonical exercise signalling pathways. Furthermore, high intensity exercise in mice and contraction of myotubes and isolated muscles led to the phosphorylation of β‐cateninS675, and this was impaired by Rac1 inhibition. Moderate intensity exercise in control and Rac1 muscle‐specific knockout mice did not induce muscle β‐cateninS675 phosphorylation, suggesting exercise intensity‐dependent regulation of β‐cateninS675. Introduction of a non‐phosphorylatable S675A mutant of β‐catenin into myoblasts impaired GLUT4 translocation and actin remodelling stimulated by carbachol, a Rac1 and RhoA activator. Exercise‐induced increases in cross‐sectional phalloidin staining (F‐actin marker) of gastrocnemius muscle was impaired in muscle from BCAT‐mKO mice. Collectively our findings suggest that β‐catenin is required for optimal glucose transport in muscle during exercise/contraction, potentially via facilitating actin cytoskeleton remodelling.

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“…These findings are consistent with those of our previous reports. 3,4) Recently, we have reported that Rac1 upregulation may be involved in augmented BSM contractions of Chal. mice.…”

Section: Resultsmentioning

confidence: 99%

“…2) Recently, we have demonstrated that Rac1 protein plays crucial role in G protein-coupled receptor (GPCR)-induced bronchial smooth muscle (BSM) contractions. 3) Further, we reported that Rac1 upregulation may be involved in augmented BSM contractions of repeatedly antigen-challenged (Chal.) mice.…”

Section: Introductionmentioning

confidence: 95%

Increased Rac1 Activation in the Enhanced Carbachol-Induced Bronchial Smooth Muscle Contraction of Repeatedly Antigen-Challenged Mice

Kai

Motegi

Suzuki

et al. 2019

Biological & Pharmaceutical Bulletin

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Recently, we demonstrated that Rac1 upregulation is involved in augmented bronchial smooth muscle (BSM) contractions of antigen-challenged mice. However, change in G protein-coupled receptor (GPCR)induced Rac1 activation remains unknown in BSMs of repeatedly antigen-challenged (Chal.) mice. We here examined carbachol (CCh)-induced Rac1 activation in BSMs of Chal. mice. Gene expression levels of both Rac1 and Rac-guanine nucleotide exchange factors (GEFs), such as Tiam1 and Trio, were increased in BSMs of Chal. mice. Furthermore, CCh-induced Rac1 activation was inhibited by pretreatment with Rac1-GEF inhibitor NSC23766 and Rac1 inhibitor EHT1864 in BSMs of sensitized-control (S.C.) and Chal. mice. Compared with S.C. mice, CCh-induced Rac1 activation was increased in BSMs of Chal. mice. In conclusion, we reported that increased CCh-induced Rac1 activation via Tiam1 and Trio upregulation, in addition to upregulate Rac1, may be involved in increased CCh-induced BSM contractions in Chal. mice.

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Up‐regulation of Rac1 in the bronchial smooth muscle of murine experimental asthma

Cited by 10 publications

References 26 publications

Rac1, A Potential Target for Tumor Therapy

Rac1, A Potential Target for Tumor Therapy

β‐Catenin is required for optimal exercise‐ and contraction‐stimulated skeletal muscle glucose uptake

Increased Rac1 Activation in the Enhanced Carbachol-Induced Bronchial Smooth Muscle Contraction of Repeatedly Antigen-Challenged Mice

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