circELP2 reverse-splicing biogenesis and function as a pro-fibrogenic factor by targeting mitochondrial quality...

Area of Science:

• Molecular Biology
• Cell Biology
• Pulmonary Medicine

Background:

• Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with unknown mechanisms.
• Fibroblast activation and extracellular matrix deposition are key features of pulmonary fibrosis.

Purpose of the Study:

• To investigate the role of circELP2 in pulmonary fibrosis.
• To elucidate the biogenesis and regulatory mechanism of circELP2.
• To evaluate circELP2 as a therapeutic target for IPF.

Main Methods:

• Investigated circELP2 biogenesis initiated by heterogeneous nuclear ribonucleoprotein L.
• Examined circELP2's function in fibroblast proliferation, migration, and extracellular matrix deposition.
• Utilized mechanistic studies to explore the circELP2-miR-630-YAP1/TAZ pathway.
• Employed adenovirus vectors for in vivo therapeutic evaluation in mice.

Main Results:

• circELP2 promotes pulmonary fibrogenesis by activating fibroblast proliferation and extracellular matrix deposition.
• Cytoplasmic circELP2 sponges miR-630, upregulating YAP1 and TAZ.
• YAP1/TAZ regulate mitochondrial quality control pathway genes (mTOR, Raptor, mLST8).
• In vivo blocking of the circELP2 pathway alleviated pulmonary fibrosis in mice.

Conclusions:

• circELP2 plays a critical role in promoting pulmonary fibrosis.
• The circELP2-miR-630-YAP1/TAZ-mitochondrial quality control pathway is a key mechanism in lung fibrosis.
• Blocking circELP2 offers a potential therapeutic strategy for treating lung fibrosis.