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286 results on '"Guo, Fukun"'

61. Rational targeting Cdc42 restrains Th2 cell differentiation and prevents allergic airway inflammation.

Author

Yang, Jun‐Qi, Kalim, Khalid W., Li, Yuan, Duan, Xin, Nguyen, Phuong, Khurana Hershey, Gurjit K., Kroner, John, Ruff, Brandy, Zhang, Li, Salomonis, Nathan, Rochman, Mark, Wen, Ting, Zheng, Yi, and Guo, Fukun

Subjects
CELL differentiation, ASTHMA prevention, INFLAMMATION prevention, ASTHMA treatment, GUANOSINE triphosphatase, CYTOSKELETON, CELL proliferation
Abstract

Summary: Background: Asthma is an allergic airway inflammation‐driven disease that affects more than 300 million people world‐wide. Targeted therapies for asthma are largely lacking. Although asthma symptoms can be prevented from worsening, asthma development cannot be prevented. Cdc42 GTPase has been shown to regulate actin cytoskeleton, cell proliferation and survival. Objectives: To investigate the role and targeting of Cdc42 in Th2 cell differentiation and Th2‐mediated allergic airway inflammation. Methods: Post‐thymic Cdc42‐deficient mice were generated by crossing Cdc42flox/flox mice with dLckicre transgenic mice in which Cre expression is driven by distal Lck promoter. Effects of post‐thymic Cdc42 deletion and pharmacological targeting Cdc42 on Th2 cell differentiation were evaluated in vitro under Th2‐polarized culture conditions. Effects of post‐thymic Cdc42 deletion and pharmacological targeting Cdc42 on allergic airway inflammation were evaluated in ovalbumin‐ and/or house dust mite‐induced mouse models of asthma. Results: Post‐thymic deletion of Cdc42 led to reduced peripheral CD8+ T cells and attenuated Th2 cell differentiation, with no effect on closely related Th1, Th17 and induced regulatory T (iTreg) cells. Post‐thymic Cdc42 deficiency ameliorated allergic airway inflammation. The selective inhibition of Th2 cell differentiation by post‐thymic deletion of Cdc42 was recapitulated by pharmacological targeting of Cdc42 with CASIN, a Cdc42 activity‐specific chemical inhibitor. CASIN also alleviated allergic airway inflammation. CASIN‐treated Cdc42‐deficient mice showed comparable allergic airway inflammation to vehicle‐treated Cdc42‐deficient mice, indicative of negligible off‐target effect of CASIN. CASIN had no effect on established allergic airway inflammation. Conclusion and Clinical Relevance: Cdc42 is required for Th2 cell differentiation and allergic airway inflammation, and rational targeting Cdc42 may serve as a preventive but not therapeutic approach for asthma control. [ABSTRACT FROM AUTHOR]

Published
2019
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65. mDia1 and Cdc42 Regulate Activin B‐Induced Migration of Bone Marrow‐Derived Mesenchymal Stromal Cells

Author

Wang, Xueer, Tang, Pei, Guo, Fukun, Zhang, Min, Yan, Yuan, Huang, Mianbo, Chen, Yinghua, Zhang, Lu, and Zhang, Lin

Abstract

In a previous study, we have shown that Activin B is a potent chemoattractant for bone marrow‐derived mesenchymal stromal cells (BMSCs). As such, the combination of Activin B and BMSCs significantly accelerated rat skin wound healing. In another study, we showed that RhoA activation plays a key role in Activin B‐induced BMSC migration. However, the role of the immediate downstream effectors of RhoA in this process is unclear. Here, we demonstrated that mammalian homolog of Drosophila diaphanous‐1 (mDia1), a downstream effector of RhoA, exerts a crucial function in Activin B‐induced BMSC migration by promoting membrane ruffling, microtubule morphology, and adhesion signaling dynamics. Furthermore, we showed that Activin B does not change Rac1 activity but increases Cdc42 activity in BMSCs. Inactivation of Cdc42 inhibited Activin B‐stimulated Golgi reorientation and the cell migration of BMSCs. Furthermore, knockdown of mDia1 affected Activin B‐induced BMSC‐mediated wound healing in vivo. In conclusion, this study demonstrated that the RhoA‐mDia1 and Cdc42 pathways regulate Activin B‐induced BMSC migration. This study may help to optimize clinical MSC‐based transplantation strategies to promote skin wound healing. Stem Cells2019;37:150–162 The RhoA‐mDia1 pathway regulates Activin B‐induced BMSC migration by promoting membrane ruffling, microtubule morphology and focal adhesion signaling dynamics. Cdc42 mediates Activin B‐induced Golgi complex polarization at the leading edge of moving BMSCs. mDia1 is involved in the wound healing process mediated by BMSCs and induced by Activin B.

Published
2019
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67. Abstract 2059: Novel roles for GNA13 and RHOA as tumor suppressor genes

Author

O'hayre, Morgan, primary, Inoue, Asuka, additional, Sales, Katiuchia, additional, Kufareva, Irina, additional, Callejas Valera, Juan Luis, additional, Guo, Fukun, additional, Mikelis, Constantinos, additional, DiPasquale, Giovanni, additional, Finkel, Kira, additional, Aoki, Junken, additional, Zheng, Yi, additional, Bugge, Thomas H., additional, and Gutkind, J. Silvio, additional

Published
2015
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