Dataset Information

HMGB1/autophagy pathway mediates the atrophic effect of TGF-?1 in denervated skeletal muscle.

ABSTRACT:

Background

Transforming growth factor beta 1 (TGF-?1) is a classical modulator of skeletal muscle and regulates several processes, such as myogenesis, regeneration and muscle function in skeletal muscle diseases. Skeletal muscle atrophy, characterized by the loss of muscle strength and mass, is one of the pathological conditions regulated by TGF-?1, but the underlying mechanism involved in the atrophic effects of TGF-?1 is not fully understood.

Methods

Mice sciatic nerve transection model was created and gastrocnemius were analysed by western blot, immunofluorescence staining and fibre diameter quantification after 2 weeks. Exogenous TGF-?1 was administrated and high-mobility group box-1 (HMGB1), autophagy were blocked by siRNA and chloroquine (CQ) respectively to explore the mechanism of the atrophic effect of TGF-?1 in denervated muscle. Similar methods were performed in C2C12 cells.

Results

We found that TGF-?1 was induced in denervated muscle and it could promote atrophy of skeletal muscle both in vivo and in vitro, up-regulated HMGB1 and increased autophagy activity were also detected in denervated muscle and were further promoted by exogenous TGF-?1. The atrophic effect of TGF-?1 could be inhibited when HMGB1/autophagy pathway was blocked.

Conclusions

Thus, our data revealed that TGF-?1 is a vital regulatory factor in denervated skeletal muscle in which HMGB1/ autophagy pathway mediates the atrophic effect of TGF-?1. Our findings confirmed a new pathway in denervation-induced skeletal muscle atrophy and it may be a novel therapeutic target for patients with muscle atrophy after peripheral nerve injury.

SUBMITTER: Yang X

PROVIDER: S-EPMC6286536 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

HMGB1/autophagy pathway mediates the atrophic effect of TGF-β1 in denervated skeletal muscle.

Yang Xiaofan X Xue Pingping P Liu Xin X Xu Xiang X Chen Zhenbing Z Chen Zhenbing Z

Cell communication and signaling : CCS 20181207 1

<h4>Background</h4>Transforming growth factor beta 1 (TGF-β1) is a classical modulator of skeletal muscle and regulates several processes, such as myogenesis, regeneration and muscle function in skeletal muscle diseases. Skeletal muscle atrophy, characterized by the loss of muscle strength and mass, is one of the pathological conditions regulated by TGF-β1, but the underlying mechanism involved in the atrophic effects of TGF-β1 is not fully understood.<h4>Methods</h4>Mice sciatic nerve transecti ...[more]

PMID: 30526602

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