MOBT Alleviates Pulmonary Fibrosis through an lncITPF-hnRNP-l-Complex-Mediated Signaling Pathway

Area of Science:

• Biomedical Research
• Molecular Biology
• Pharmacology

Background:

• Pulmonary fibrosis involves irreversible lung scarring with limited treatment options.
• Current therapies for pulmonary fibrosis are insufficient, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the anti-pulmonary fibrosis effects of 3-(4-methoxyphenyl)-4-oxo-4H-1-benzopyran-7-yl(αS)-α,3,4-trihydroxybenzenepropanoate (MOBT).
• To elucidate the molecular mechanism underlying MOBT's therapeutic action in pulmonary fibrosis models.

Main Methods:

• Utilized bleomycin and transforming growth factor-β1 induced mouse and cell models of pulmonary fibrosis.
• Employed MicroCT imaging, lung function tests, histological staining (H&E, Masson), and molecular biology techniques (FISH, ChIP-PCR, RIP, ChIP-seq, RNA-seq).

Main Results:

• MOBT demonstrated significant anti-pulmonary fibrosis activity in preclinical models.
• MOBT inhibited lncITPF transcription by blocking p-Smad2/3 nuclear translocation, reducing the lncITPF-hnRNP L complex.
• This mechanism led to decreased MEF2c expression via alternative splicing inhibition, impacting downstream targets like TAGLN2 and FMN1.

Conclusions:

• MOBT alleviates pulmonary fibrosis by modulating the lncITPF-hnRNP L complex-targeted MEF2c signaling pathway.
• MOBT represents a potential new drug candidate and therapeutic target for treating pulmonary fibrosis.