TAZ Activator Is Involved in IL-10-Mediated Muscle Responses in an Animal Model of Traumatic Brain Injury.

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.

• Authors: Ruyi Zou, Da Li, Gang Wang, Mo Zhang, Yili Zhao, Zeyu Yang
• Journal: Inflammation (Inflammation) Vol. 40 Issue 1 Pg. 100-105 (Feb 2017) ISSN: 1573-2576 [Electronic] United States
• PMID: 27718096 (Publication Type: Journal Article)

Chemical References

• Cytokines
• IBS008738
• Imidazoles
• Transcription Factors
• Interleukin-10
• Acyltransferases
• tafazzin protein, mouse

Topics

• Acyltransferases
• Animals
• Brain Injuries, Traumatic (pathology)
• Cell Line
• Cytokines (drug effects)
• Imidazoles (classification, pharmacology, therapeutic use)
• Inflammation
• Interleukin-10 (metabolism, physiology)
• Macrophages (drug effects, pathology)
• Mice
• Models, Animal
• Muscular Atrophy (drug therapy, etiology)
• Transcription Factors (agonists, physiology)