Browsing by Author "Zhao, Z."

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    Correlation of BAG-3 and Heat Shock Protein 70 with CD30 expression in T-cell Lymphomas
    (Springer Nature, 2014-02-04) Jiang, L.; Zhao, Z.; Menke, D. M.; Rizzo, K. A.; Pathology and Laboratory Medicine, School of Medicine
    T-cell lymphomas are aggressive lymphomas with decreased prognosis and resistance to therapy. BAG-3 and heat shock protein 70 (HSP70) function in chemotherapeutic resistance and cellular survival. Expression of BAG-3 has not been investigated in T cell lymphomas. We investigated fifty cases including benign, systemic and cutaneous T cell lymphomas. Benign T cells were negative for BAG-3 and HSP70 immunohistochemical staining. BAG-3 expression correlated with increased HSP70 expression in a subset of systemic T cell lymphoma cases co-expressing the CD30 antigen. Correlation between BAG-3, HSP70 and CD30 expression was not seen in cutaneous T cell lymphoma cases. However, these cases showed a significant increase in BAG-3 staining when compared to CD30 negative systemic T cell lymphoma cases. The differential protein expression profile of BAG-3 and HSP70 may indicate a specific role for these proteins and the ubiquitin-proteasome system/autophagy in T cell lymphomas which may help guide future targeted therapy.
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    Mechanical Regulation of Bone Homeostasis Through p130Cas-mediated Alleviation of NF-κB Activity
    (American Association for the Advancement of Science, 2019-09) Miyazaki, T.; Zhao, Z.; Ichihara, Y.; Yoshino, D.; Imamura, T.; Sawada, K.; Hayano, S.; Kamioka, H.; Mori, S.; Hirata, H.; Araki, K.; Kawauchi, K.; Shigemoto, K.; Tanaka, S.; Bonewald, L. F.; Honda, H.; Shinohara, M.; Nagao, M.; Ogata, T.; Harada, I.; Sawada, Y.; Medicine, School of Medicine
    Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading-mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB-mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress-dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas-NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.