Abstract
The transcriptional coactivator with PDZ-binding motif (TAZ) functions as a downstream regulatory target in the Hippo signaling pathway that plays various roles. We previously developed a cell-based assay and identified the TAZ activator IBS008738 as a potential therapeutic target for glucocorticoid-induced atrophy. To further explore the application of IBS008738 in various muscle-related diseases, we examined the function of IBS008738 in inflammatory cytokine-mediated mouse muscle responses after traumatic brain injury (TBI). Preliminary screening suggested that IBS008738 treatments increased the levels of IL-10 in C2C12 cells. In TBI and sham control mice, we compared the effect of IBS008738 treatments on TNF α, IL-6, and IL-10 mRNA levels, muscle morphologic changes, and macrophage phenotype changes. Our findings support that the TAZ activator IBS008738 decreases muscle wasting by upregulating IL-10 and inhibiting TNF α and IL-6, and this process is implemented by changing the macrophage phenotypes. These results indicate a new mechanism of the TAZ activator as a potential therapy for atrophy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Jeong, H., S. Bae, S.Y. An, M.R. Byun, J.H. Hwang, M.B. Yaffe, J.H. Hong, and E.S. Hwang. 2010. TAZ as a novel enhancer of MyoD-mediated myogenic differentiation. FASEB Journal 24: 3310–3320.
Hong, J.H., and M.B. Yaffe. 2006. TAZ: a beta-catenin-like molecule that regulates mesenchymal stem cell differentiation. Cell Cycle 5: 176–179.
Gabriel, B.M., D.L. Hamilton, A.M. Tremblay, and H. Wackerhage. 2016. The Hippo signal transduction network for exercise physiologists. Journal of Applied Physiology 120: 1105–1117.
Yang, Z., K. Nakagawa, A. Sarkar, J. Maruyama, H. Iwasa, Y. Bao, M. Ishigami-Yuasa, S. Ito, H. Kagechika, S. Hata, H. Nishina, S. Abe, M. Kitagawa, and Y. Hata. 2014. Screening with a novel cell-based assay for TAZ activators identifies a compound that enhances myogenesis in C2C12 cells and facilitatesmuscle repair in a muscle injury model. Molecular and Cellular Biology 34: 1607–1621.
Park, G.H., H. Jeong, M.G. Jeong, E.J. Jang, M.A. Bae, Y.L. Lee, N.J. Kim, J.H. Hong, and E.S. Hwang. 2014. Novel TAZ modulators enhance myogenic differentiation and muscle regeneration. British Journal of Pharmacology 171: 4051–4061.
Jang, E.J., H. Jeong, J.O. Kang, N.J. Kim, M.S. Kim, S.H. Choi, S.E. Yoo, J.H. Hong, M.A. Bae, and E.S. Hwang. 2012. TM-25659 enhances osteogenic differentiation and suppresses adipogenic differentiation by modulating the transcriptional co-activator TAZ. British Journal of Pharmacology 165: 1584–1594.
Cisterna, B.A., C. Cardozo, and J.C. Sáez. 2014. Neuronal involvement in muscular atrophy. Frontiers in Cellular Neuroscience 8: article 405.
Cohen, S., J.A. Nathan, and A.L. Goldberg. 2015. Muscle wasting in disease: molecular mechanisms and promising therapies. Nature Reviews Drug Discovery 14: 58–74.
Palus, S., S. von Haehling, and J. Springer. 2014. Muscle wasting: an overview of recent developments in basic research. International Journal of Cardiology 176: 640–644.
Meador, B.M., C.P. Krzyszton, R.W. Johnson, and K.A. Huey. 2008. Effects of IL-10 and age on IL-6, IL-1beta, and TNF-alpha responses in mouse skeletal and cardiac muscle to an acute inflammatory insult. Journal of Applied Physiology 104: 991–997.
Tidball, J.G., and S.A. Villalta. 2010. Regulatory interactions between muscle and the immune system during muscle regeneration. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 298: R1173–R1187.
Bencze, M., E. Negroni, D. Vallese, H. Yacoub-Youssef, S. Chaouch, A. Wolff, A. Aamiri, J.P. Di Santo, B. Chazaud, G. Butler-Browne, W. Savino, V. Mouly, and Riederer. 2012. Proinflammatory macrophages enhance the regenerative capacity of human myoblasts by modifying their kinetics of proliferation and differentiation. Molecular Therapy 20: 2168–2179.
Deng, B., M. Wehling-Henricks, S.A. Villalta, Y. Wang, and J.G. Tidball. 2012. IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration. Journal of Immunology 189: 3669–3680.
Zoranovic, T., L. Grmai, and E.A. Bach. 2013. Regulation of proliferation, cell competition, and cellular growth by the Drosophila JAK-STAT pathway. JAKSTAT 2: e25408.
Carey, A.J., C.K. Tan, and G.C. Ulett. 2012. Infection-induced IL-10 and JAK-STAT: a review of the molecular circuitry controlling immune hyperactivity in response to pathogenic microbes. JAKSTAT 1: 159–167.
Karin, M., and H. Clevers. 2016. Reparative inflammation takes charge of tissue regeneration. Nature 529: 307–315.
Li, L.Z., Y.J. Bao, and M. Zhao. 2011. 17beta-estradiol attenuates programmed cell death in cortical pericontusional zone following traumatic brain injury via upregulation of ERalpha and inhibition of caspase-3 activation. Neurochemistry International 58: 126–133.
Ehmer, U., and J. Sage. 2016. Control of proliferation and cancer growth by the hippo signaling pathway. Molecular Cancer Research 14: 127–140.
Yu, F.X., B. Zhao, and K.L. Guan. 2015. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell 163: 811–828.
Bao, Y., Y. Hata, M. Ikeda, and K. Withanage. 2011. Mammalian Hippo pathway: from development to cancer and beyond. Journal of Biochemistry 149: 361–379.
Pan, D. 2010. The Hippo signaling pathway in development and cancer. Developmental Cell 19: 491–505.
Kodaka, M., Z. Yang, K. Nakagawa, J. Maruyama, X. Xu, A. Sarkar, A. Ichimura, Y. Nasu, T. Ozawa, H. Iwasa, M. Ishigami-Yuasa, S. Ito, H. Kagechika, and Y. Hata. 2015. A new cell-based assay to evaluate myogenesis in mouse myoblast C2C12 cells. Experimental Cell Research 336: 171–181.
Kawano, S., J. Maruyama, S. Nagashima, K. Inami, W. Qiu, H. Iwasa, K. Nakagawa, M. Ishigami-Yuasa, H. Kagechika, H. Nishina, and Y. Hata. 2015. A cell-based screening for TAZ activators identifies ethacridine, a widely used antiseptic and abortifacient, as a compound that promotes dephosphorylation of TAZ and inhibits adipogenesis in C3H10T1/2 cells. Journal of Biochemistry 158: 413–423.
Nitahara-Kasahara, Y., H. Hayashita-Kinoh, T. Chiyo, A. Nishiyama, H. Okada, S. Takeda, and T. Okada. 2014. Dystrophic mdx mice develop severe cardiac and respiratory dysfunction following genetic ablation of the anti-inflammatory cytokine IL-10. Human Molecular Genetics 23: 3990–4000.
Ruffell, D., F. Mourkioti, A. Gambardella, P. Kirstetter, R.G. Lopez, N. Rosenthal, and C. Nerlov. 2009. A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair. Proceedings of the National Academy of Sciences of the United States of America 106: 17475–17480.
Acknowledgments
We are grateful for Hata Yutaka (Tokyo Medical and Dental University) for materials and advice. This study was supported by Grant from the National Natural Science Foundation of China (No. 81401143).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All experiments were done according to the international and institutional guidelines for animal care, and all experimental procedures were approved by the Animal Care and Use Committee of China Medical University (protocol number 2014PS28K).
Conflict of Interest
The authors declare that they have no conflicts of interest.
ELECTRONIC SUPPLEMENTARY MATERIAL
Below is the link to the electronic supplementary material.
Supplementary Table S1
(XLS 26 kb)
Rights and permissions
About this article
Cite this article
Zou, R., Li, D., Wang, G. et al. TAZ Activator Is Involved in IL-10-Mediated Muscle Responses in an Animal Model of Traumatic Brain Injury. Inflammation 40, 100–105 (2017). https://doi.org/10.1007/s10753-016-0457-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-016-0457-5