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

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

  • Cell Commun Signal. 2018 Dec 7;16(1):97. doi: 10.1186/s12964-018-0310-6.
Xiaofan Yang 1 Pingping Xue 2 Xin Liu 3 Xiang Xu 1 Zhenbing Chen 4
Affiliations

Affiliations

  • 1 Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 3 Department of Anesthesiology, The People's Hospital of Hanchuan, Renmin Hospital of Wuhan University, Hanchuan, 432300, Hubei Province, China.
  • 4 Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. zhenbingchen1968@163.com.
Abstract

Background: 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.

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-β1 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-β1 in denervated muscle. Similar methods were performed in C2C12 cells.

Results: We found that TGF-β1 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-β1. The atrophic effect of TGF-β1 could be inhibited when HMGB1/Autophagy pathway was blocked.

Conclusions: Thus, our data revealed that TGF-β1 is a vital regulatory factor in denervated skeletal muscle in which HMGB1/ Autophagy pathway mediates the atrophic effect of TGF-β1. 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.

Keywords

Atrophy; Autophagy; Denervation; HMGB1; Skeletal muscle; TGF-β1.

Figures
Products