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tgf-β signaling in aortic aneurysm: another round of controversy

Journal of Genetics and Genomics 2010年第9期37卷 583-591页

作者： Fuyu Lin Xiao Yang State Key Laboratory of Proteomics Genetic Laboratory of Development and Diseases Institute of Biotechnology Beijing 100071 China

Aortic aneurysm （AA） is a common health problem with high mortality and no effective drugs. Transforming growth factor-β （tgf-β） superfamily members regulate various cellular processes, and tgf-β signaling has key roles in development, tissue homeo- stasis, and diseases. Interest in the role of tgf-β signaling in the pathogenesis of AAs has recently emerged, particularly since genetic studies demonstrated an association between gene mutations in components of tgf-β signaling and AAs. However, paradoxical discoveries have implicated dysregulated tgf-β signaling in aneurysm formation, complicating the precise functional role for tgf-β in aneurysm development and progression. Furthermore, interventions targeting towards tgf-β signaling using losartan, which may represent a suitable therapeutic option for AAs, were subject to skepticism especially because of conflicting experimental results obtained from tgf-β antibody treatment without knowledge of the underlying mechanism. We propose a tgf-β aneurysm paradox, which would provide a good opportunity for the development of genetic mouse models of AA. These models would be used to clarify the mechanisms underlying tgf-β signaling, which would translate into novel pharmacologic therapies based on the new molecular discoveries.

关键词： aneurysm tgf-β signaling mouse model

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WDR74 functions as a novel coactivator in tgf-β signaling

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Journal of Genetics and Genomics 2018年第12期45卷 639-650页

作者： Jinquan Liu Meiling Zhao Bo Yuan Shuchen Gu Mingjie Zheng Jian Zou Jianping Jin Ting Liu Xin-Hua Feng MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell signaling Network Life Sciences Institute Zhejiang University Department of Biochemistry and Molecular Biology University of Texas Health Science Center at Houston Institute of Translational Medicine School of Medicine Zhejiang University Department of Cell Biology School of Medicine Zhejiang University Department of Molecular & Cellular Biology and Michael DeBakey Department of Surgery Baylor College of Medicine

Smads are critical intracellular signal transducers for transforming growth factor-β(tgf-β) in mammalian cells. In this study, we have identified WD repeat-containing protein 74(WDR74) as a novel transcriptional coactivator for Smads in the canonical tgf-β signaling pathway. Through direct interactions with Smad proteins, WDR74 enhances tgf-β-mediated phosphorylation and nuclear accumulation of Smad2 and Smad3. Consequently, WDR74 enables stronger transcriptional responses and more robust tgf-β-induced physiological responses. Our findings have elucidated a critical role of WDR74 in regulating tgf-β signaling.

关键词： WDR74 tgf-β signaling Transcription Growth inhibition EMT

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Increase of CD4^+CD25^+ T cells in Smad3^(-/-) mice

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World Journal of Gastroenterology 2006年第15期12卷 2455-2458页

作者： Zi-Bing Wang Yu-Fang Cui Yu-Qing Liu Wei Jin Han Xu Zhu-Jun Jiang Ya-Xin Lu Ying Zhang Xiao-Lan Liu Bo Dong Department of Immunology Beijing Institute of Radiation Medicine 27 Taiping Road Beijing 100850 China Third Affiliated Hospital of Xinxiang Medical College Xinxiang 453003 Henan Province China Institute of Biotechnology Beijing 100071 China

AIM： To investigate the changes of lymphocyte subpopulations, especially CD4^＋CD25^ T regulatory cells in Smad3^-/- mice. METHODS： Hematological changes and changes of lymphocyte subpopulations were detected in Smad3＂/- mice using cell counter and flow cytometry, respectively, and compared to their littermate controls. RESULTS： The numbers of neutrophils and lymphocytes in peripheral blood were significantly increased in Smad3^-/- mice compared to littermate controls. CD19^＋ expressing cells in blood and spleen, and CD8^＋ T cells in thymus were all markedly decreased in Smad3^-/- mice. More important, Smad3^-/- mice had an increased population of CD4^＋CD25^＋ T cells in peripheral lymphoid tissues, including thymus, spleen, and lymph nodes. CONCLUSION： These observations suggest that the changes of lymphocyte subpopulations might play a role in susceptibility to inflammation of Smad3^-/- mice.

关键词： CD4^+CD25^+ T cells Lymphocyte subpopulation SMAD3 tgf-β signaling

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