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949?��?178?arb. units, P?=?0.014; Figure?2A) and protein expression (0.94?��?0.09 vs. 1.69?��?0.29?arb. units, P?=?0.013; Figure?2B) of FNDC5 when compared with saline-infused mice, respectively. In addition, a lower PGC-1�� mRNA expression was evident in Ang-II compared with saline-infused mice (89?��?15 vs. 224?��?48?arb. units, P?=?0.004; Figure?2C), which was correlated (r?=?0.82, P?Enzalutamide muscle fibronectin type III domain containing 5 Compared with saline-injected mice, the TNF-��-injected group had a 53% reduction in FNDC5 at the mRNA level (337?��?70 vs. 158?��?25?arb. units, P?=?0.026; www.selleckchem.com/products/abt-199.html Figure?3A) and a 28% reduction (P?Histone demethylase (con) and animals injected tumour necrosis factor-�� (TNF-��) intraperitoneally ... Impact of angiotensin II and cytokines on C2C12 myotube fibronectin type III domain containing 5 expression Compared with control, incubating C2C12 myotubes with TNF-��, IL-1?, or a combination of both resulted in a significant reduction of FNDC5 and PGC-1�� mRNA expression, while, in contrast, Ang-II and IFN-�� had no influence (Figure?4A and ?and4B).4B). This resulted in a positive correlation between mRNA expression of PGC-1�� and FNDC5 (r?=?0.68, P?=?0.0001; Figure?4C). Figure 4 Quantitative evaluation of (A) fibronectin type III domain containing 5 (FNDC5) and (B) PGC-1�� in C2C12 myotubes incubated either with angiotensin II (Ang-II), tumour necrosis factor-�� (TNF-��), interleukin (IL)-1?, ��-interferon ... The cytokine-induced down-regulation of FNDC5 mRNA expression could be prevented by blocking the Akt, PKC, or the STAT-3 activation by specific inhibitors (Figure?5A�CC). Blocking the activation of the p42/44 MAPK or c-Jun N-terminal kinase no effect on cytokine-induced FNDC5 down-regulation was evident (Figure?5D and ?and5E).5E). The blockage of the p38 MAPK activation only prevented the IL-1?-induced FNDC5 down-regulation, whereas the TNF-��-induced modulation of FNDC5 expression was not affected.