TGF-β requires the activation of canonical and non-canonical signalling pathways to induce skeletal muscle atrophy

被引：47

作者：

Abrigo, Johanna ^{[2
,3
,4
]}

Campos, Fabian ^{[2
,3
,4
]}

Simon, Felipe ^{[2
,3
,4
]}

Riedel, Claudia ^{[2
,3
,4
]}

Cabrera, Daniel ^{[5
,6
]}

Vilos, Cristian ^{[7
,8
]}

Cabello-Verrugio, Claudio ^{[1
,2
,3
,9
]}

机构：

[1] Univ Andres Bello, Fac Ciencias Biol, Dept Ciencias Biol, Lab Muscle Pathol Fragil & Aging, Ave Republ 239, Santiago 8370146, Chile

[2] Univ Andres Bello, Fac Med, Ave Republ 239, Santiago 8370146, Chile

[3] Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile

[4] Univ Andres Bello, Fac Ciencias Biol, Dept Ciencias Biol, Ave Republ 239, Santiago 8370146, Chile

[5] Univ Bernardo O Higgins, Fac Salud, Dept Ciencias Quim & Biol, Santiago 8370993, Chile

[6] Pontificia Univ Catolica Chile, Fac Med, Dept Gastroenterol, Santiago 8331150, Chile

[7] Univ Andres Bello, Fac Med, Ctr Integrat Med & Innovat Sci, Lab Nanomed & Targeted Delivery, Santiago 8370146, Chile

[8] Univ Andres Bello, Ctr Bioinformat & Integrat Biol, Fac Biol Sci, Santiago 8370146, Chile

[9] Univ Santiago Chile, Ctr Dev Nanosci & Nanotechnol CEDENNA, Santiago 9170022, Chile

来源：

BIOLOGICAL CHEMISTRY | 2018年 / 399卷 / 03期

关键词：

MAPK; MuRF-1; muscle atrophy; reactive oxygen species; Smad; GROWTH-FACTOR-BETA; POLYMERASE CHAIN-REACTION; ANGIOTENSIN-II; PROTEIN-DEGRADATION; FIBROTIC RESPONSE; EXPRESSION; MECHANISMS; FIBROSIS; DECORIN; ALPHA;

D O I：

10.1515/hsz-2017-0217

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The transforming growth factor type-beta (TGF-beta) induces skeletal muscle atrophy characterised by a decrease in the fibre's diameter and levels of myosin heavy chain (MHC), also as an increase of MuRF-1 expression. In addition, TGF-beta induces muscle atrophy by a mechanism dependent on reactive oxygen species (ROS). TGF-beta signals by activating both canonical Smad-dependent, and non-canonical signalling pathways such as ERK1/2, JNK1/2, and p38 MAPKs. However, the participation of canonical and non-canonical signalling pathways in the TGF-beta atrophic effect on skeletal muscle is unknown. We evaluate the impact of Smad and MAPK signalling pathways on the TGF-beta-induced atrophic effect in C2C12 myotubes. The results indicate that TGF-beta activates Smad2/3, ERK1/2 and JNK1/2, but not p38 in myotubes. The pharmacological inhibition of Smad3, ERK1/2 and JNK1/2 activation completely abolished the atrophic effect of TGF-beta. Finally, the inhibition of these canonical and non-canonical pathways did not decrease the ROS increment, while the inhibition of ROS production entirely abolished the phosphorylation of Smad3, ERK1/2 and JNK1/2. These results suggest that TGF-beta requires Smad3, ERK1/2 and JNK1/2 activation to produce skeletal muscle atrophy. Moreover, the induction of ROS by TGF-beta is an upstream event to canonical and non-canonical pathways.

引用

页码：253 / 264

页数：12

共 49 条

[1] Transforming growth factor type beta (TGF-β) requires reactive oxygen species to induce skeletal muscle atrophy [J].