title: 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.affiliation: Department of Neurosurgery, General Hospital of Benxi Iron and Steel CO. LTD, Benxi, 117000, China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Zou
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
authors.forename: Da
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Urology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, 23507, VA, USA.
authors.forename: Yili
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Ultrasound, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, China. yangzy1@sj-hospital.org.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000217:Acyltransferases; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000473:pathology*; D002460:Cell Line; D016207:Cytokines / Q000187:drug effects; D007093:Imidazoles / Q000145:classification* / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D023421:Models, Animal; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000209:etiology; D014157:Transcription Factors / Q000819:agonists* / Q000502:physiology
chemical_list: D016207:Cytokines; C000588695:IBS008738; D007093:Imidazoles; D014157:Transcription Factors; D016753:Interleukin-10; D000217:Acyltransferases; C486363:tafazzin protein, mouse
keywords: interleukin-10; macrophage; muscle responses; traumatic brain injury