Year: 2018
Type: article
Abstract: Age-related muscle atrophy (sarcopenia) is the leading cause for disability in aged population, but the underlying molecular mechanisms are poorly understood. Here we identify a novel role for the secreted glycoprotein Dickkopf 3 (Dkk3) in sarcopenia. Forced expression of Dkk3 in muscles in young mice leads to muscle atrophy. Conversely, reducing its expression in old muscles restores both muscle size and function. Dkk3 induces nuclear import of β-catenin and enhances its interaction with FoxO3, which in turn activates the transcription of E3 ubiquitin ligase Fbxo32 and Trim63, driving muscle atrophy. These findings suggest that Dkk3 may be used as diagnostic marker and as therapeutic target for age-related muscle atrophy, and reveal a distinct transcriptional control of Fbxo32 and Trim63.
Source: Nature Communications
Authors: Jie Yin, Lele Yang, Yangli Xie, Yan Liu, Sheng Li, Wenjun Yang, Bo Xu, Hongbin Ji, Lianghua Ding, Kun Wang, Gang Li, Lin Chen, Ping Hu
Institutions: Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, State Key Laboratory of Cell Biology, Army Medical University, Daping Hospital, State Key Laboratory of Trauma, Burns and Compound Injury Research, Soochow University, Tongji University, Shanghai East Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W2806508890