Role of Rho kinase isoforms in murine allergic airway responses

Zhu, Min; Liu, Ping-Yen; Kasahara, David I.; Williams, Alison S.; Verbout, Norah G.; Halayko, Andrew J.; Fedulov, Alexey V.; Shoji, Takuhito; Williams, Erin S.; Noma, Kazuhiro; Shore, Stephanie A.; Liao, James K.

doi:10.1183/09031936.00125010

Cited by 33 publications

(58 citation statements)

References 48 publications

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“…In animal models of allergic asthma, exposition to the allergen ovalbumin (OVA) induces ROCK activation in the lungs (Zhu et al, 2011 (Zhu et al, 2011). Moreover, ROCK2, but not ROCK1, is involved in mucous cell hyperplasia in the OVA model of allergic asthma (Kasahara et al, 2015).…”

Section: B Asthmamentioning

confidence: 99%

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

Loirand¹

2015

Pharmacol Rev

154

133

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Section: B Asthmamentioning

confidence: 99%

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

Loirand¹

2015

Pharmacol Rev

154

133

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“…Data from animal models indicate that Rho-associated coiled-coil forming kinases (ROCKs), serine/threonine protein kinases activated by GTP-bound RhoA, may be involved in the pathogenesis of asthma (1-4). ROCKs have pleiotropic effects that can contribute to asthma, including the ability to augment smooth muscle contraction (5, 6), as well as effects on immune cell proliferation and migration (2, 7).…”

Section: Introductionmentioning

confidence: 99%

“…We have previously reported that both ROCK1 and ROCK2 contribute to the pathological features of allergic airways disease in mice (4). ROCK1 and ROCK2 deficient mice typically die either in utero or soon after birth (15, 16), but heterozygous mice (ROCK1 +/− and ROCK2 +/− mice) are viable (17, 18).…”

Section: Introductionmentioning

confidence: 99%

“…We have shown that ovalbumin (OVA) aerosol challenge results in ROCK activation in the airways of OVA sensitized and challenged mice (4) and both basal and OVA-induced ROCK activation are reduced by approximately 50% in ROCK1 +/− or ROCK2 +/− versus WT mice, indicating that both isoforms are activated after allergen challenge. Importantly, OVA-induced AHR was virtually abolished in both ROCK1 +/− and ROCK2 +/− versus WT mice (4). Pulmonary inflammation and goblet cell hyperplasia were also reduced in ROCK1 +/− and ROCK2 +/− versus WT mice, though there were differences in the role of each ROCK isoform, with ROCK1 insufficiency resulting in greater reductions in Th2 cytokines and lymphocyte recruitment to the airways and ROCK2 insufficiency causing greater reductions in goblet cell hyperplasia (4).…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, OVA-induced AHR was virtually abolished in both ROCK1 +/− and ROCK2 +/− versus WT mice (4). Pulmonary inflammation and goblet cell hyperplasia were also reduced in ROCK1 +/− and ROCK2 +/− versus WT mice, though there were differences in the role of each ROCK isoform, with ROCK1 insufficiency resulting in greater reductions in Th2 cytokines and lymphocyte recruitment to the airways and ROCK2 insufficiency causing greater reductions in goblet cell hyperplasia (4). …”

Section: Introductionmentioning

confidence: 99%

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Abrogation of airway hyperresponsiveness but not inflammation by rho kinase insufficiency

Kasahara¹,

Ninin²,

Wurmbrand³

et al. 2015

Clin Experimental Allergy

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Background Major features of allergic asthma include airway hyperresponsiveness (AHR), eosinophilic inflammation, and goblet cell metaplasia. Rho kinase (ROCK) is a serine/threonine protein kinase that regulates the actin cytoskeleton. By doing so, it can modulate airway smooth muscle cell contraction and leukocyte migration and proliferation. This study was designed to determine the contributions of the two ROCK isoforms, ROCK1 and ROCK2, to AHR, inflammation and goblet cell metaplasia in a mast-cell dependent model of allergic airways disease. Methods and Results Repeated intranasal challenges with OVA caused AHR, eosinophilic inflammation, and goblet cell hyperplasia in wildtype (WT) mice. OVA-induced AHR was partially or completely abrogated in mice haploinsufficient for ROCK2 (ROCK2+/−) or ROCK1 (ROCK1+/−), respectively. In contrast, there was no effect of ROCK insufficiency on allergic airways inflammation, although both ROCK1 and ROCK2 insufficiency attenuated mast cell degranulation. Goblet cell hyperplasia, as indicated by PAS staining, was not different in ROCK1+/− versus WT mice. However, in ROCK2+/− mice, goblet cell hyperplasia was reduced in medium but not large airways. Maximal acetylcholine-induced force generation was reduced in tracheal rings from ROCK1+/− and ROCK2+/− versus WT mice. The ROCK inhibitor, fasudil, also reduced airway responsiveness in OVA-challenged mice, without affecting inflammatory responses. Conclusion In a mast cell model of allergic airways disease, ROCK1 and ROCK2 both contribute to AHR, likely through direct effects on smooth muscle cell and effects on mast-cell degranulation. In addition, ROCK2 but not ROCK1 plays a role in allergen-induced goblet cell hyperplasia.

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Rho signaling research: history, current status and future directions

2018

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One of the main research areas in biology from the mid‐1980s through the 1990s was the elucidation of signaling pathways governing cell responses. These studies brought, among other molecules, the small GTPase Rho to the epicenter. Rho signaling research has since expanded to all areas of biology and medicine. Here, we describe how Rho emerged as a key molecule governing cell morphogenesis and movement, how it was linked to actin reorganization, and how the study of Rho signaling has expanded from cultured cells to whole biological systems. We then give an overview of the current research status of Rho signaling in development, brain, cardiovascular system, immunity and cancer, and discuss the future directions of Rho signaling research, with emphasis on one Rho effector, ROCK*. *The Rho GTPase family. Rho family GTPases have now expanded to contain 20 members. Amino acid sequences of 20 Rho GTPases found in human were aligned and the phylogenetic tree was generated by ClustalW2 software (EMBL‐EBI) based on NJ algorithm. The subfamilies of the Rho GTPases are highlighted by the circle and labeled on the right side. Rho cited in this review refers to the original members of Rho subfamily, RhoA, RhoB and RhoC, that are C3 substrates, and, unless specified, not to other members of the Rho subfamily such as Rac, Cdc42, and Rnd.

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Role of Rho kinase isoforms in murine allergic airway responses

Cited by 33 publications

References 48 publications

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

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

Abrogation of airway hyperresponsiveness but not inflammation by rho kinase insufficiency

Rho signaling research: history, current status and future directions

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