Subacute TGFβ expression drives inflammation, goblet cell hyperplasia, and pulmonary function abnormalities in mice...

Area of Science:

• Pulmonary Medicine
• Molecular Biology
• Genetics

Background:

• Cystic fibrosis (CF) lung disease phenotypes vary, partly independent of CFTR genotype.
• Transforming growth factor-beta (TGFβ) is a known genetic modifier of CF, but its mechanism is unclear.

Purpose of the Study:

• To investigate if TGFβ is sufficient to cause CF lung disease features in vivo.
• To determine if CFTR deficiency increases susceptibility to pathological TGFβ effects.

Main Methods:

• A CF mouse model and controls received intratracheal TGFβ1 via adenoviral vector.
• Evaluated lung mechanics, bronchoalveolar lavage fluid, histology, RNA, and protein 1 week post-treatment.

Main Results:

• Both CF and non-CF mice showed similar inflammation and goblet cell hyperplasia after TGFβ1.
• TGFβ1 induced greater lung mechanics abnormalities in CF mice, linked to PI3K/MAPK signaling.
• CFTR transcripts decreased, while ENaC transcripts increased in both groups; specific transcription factors differed.

Conclusions:

• Pulmonary TGFβ1 is sufficient to cause remodeling and lung mechanics abnormalities in mice.
• Shared and unique cell signaling pathways are activated in CF and non-CF mice by TGFβ1.
• Cellular response differences to TGFβ may contribute to CF lung pathology.