title: TNF alpha inhibits myogenic differentiation of C2C12 cells through NF-κB activation and impairment of IGF-1 signaling pathway.
abstract: Cachexia or muscle wasting is a common condition that occurs in many chronic diseases. The wasting conditions are characterized by increased levels of TNF-α which was also known as cachectin in the past. But how TNF-α exerts its cachetic effects remains controversial. To clarify this issue, we investigated the impact of TNF-α on C2C12 cell myogenic differentiation. Our results demonstrate that myotube formation was completely inhibited by TNF-α when added to differentiating C2C12 myoblasts. The inhibitory effect of TNF-α on differentiation was accompanied by activation of NF-κB and down regulation of myogenin and Akt. Importantly, TNF-α's effect on differentiation was abolished when IGF-1 was added to the culture. IGF-1 treatment also inhibited NF-κB reporter activity and restored Akt levels. Our data suggest that TNF-α inhibits myogenic differentiation through NF-κB activation and impairment of IGF-1 signaling pathway. The reversal of TNF-α induced inhibition of myogenesis by IGF-1 may have significant therapeutic potential.
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: Q
authors: Q
authors: Zhao
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: S T
authors: ST
authors: Yang
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; The Affiliated Wuxi Hospital for Maternal and Child Health Care of Medical University of Nanjing, Wuxi, Jiangsu Province, China.
authors: J J
authors: JJ
authors: Wang
authors: Department of Surgery, First Affiliated Hospital, Soochow University, Suzhou, China.
authors: J
authors: J
authors: Zhou
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: S S
authors: SS
authors: Xing
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: C C
authors: CC
authors: Shen
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: X X
authors: XX
authors: Wang
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: Y X
authors: YX
authors: Yue
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: J
authors: J
authors: Song
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: M
authors: M
authors: Chen
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: Y Y
authors: YY
authors: Wei
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: Q P
authors: QP
authors: Zhou
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors: T
authors: T
authors: Dai
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. Electronic address: yaohua_song1@yahoo.com.
authors: Y H
authors: YH
authors: Song
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D007334:Insulin-Like Growth Factor I / Q000276:immunology*; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000276:immunology; D032446:Myoblasts / Q000166:cytology* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I
keywords: C2C12; IGF-1; TNF-α