CCT7 Regulates TRAF6-Mediated Autophagy to Promote Posttraumatic Joint Contracture

Area of Science:

• Biomedical Science
• Molecular Biology
• Cellular Biology

Background:

• Posttraumatic joint contracture (PTJC) significantly limits joint motion following injury.
• The chaperonin-containing T-complex polypeptide (CCT) family is implicated in fibrotic diseases.
• Understanding the specific role of CCT family members in PTJC is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the role of CCT7 in the development of PTJC.
• To elucidate the molecular mechanisms by which CCT7 influences fibroblast behavior and fibrosis.
• To assess the therapeutic potential of targeting CCT7 in PTJC.

Main Methods:

• Quantitative analysis of CCT7 expression in PTJC tissues and TGF-β1-stimulated fibroblasts.
• CCT7 knockdown experiments in vitro and in vivo.
• Assessment of fibroblast activation markers (α-SMA, COL-I), migration, and autophagy.
• Co-immunoprecipitation to study CCT7-TRAF6 interaction and ubiquitination.
• Evaluation of joint range of motion and fibrosis markers in animal models.

Main Results:

• CCT7 expression is upregulated in PTJC tissues and TGF-β1-treated fibroblasts.
• CCT7 knockdown reduces fibroblast activation, migration, and fibrosis, while promoting autophagy (increased LC3-II, Beclin-1; decreased p62).
• CCT7 interacts with TRAF6, promoting its ubiquitination and degradation. TRAF6 knockdown reverses CCT7 knockdown-induced autophagy enhancement and worsens fibrosis.
• In vivo CCT7 knockdown improves joint mobility, reduces fibrosis markers, and enhances autophagy.

Conclusions:

• CCT7 plays a significant role in promoting PTJC by enhancing fibroblast activation and suppressing autophagy.
• CCT7 facilitates fibrosis through interaction with TRAF6, impacting its degradation.
• Targeting CCT7 represents a potential therapeutic strategy for alleviating PTJC and joint fibrosis.