Deformation-induced transitional myofibroblasts contribute to compensatory lung growth

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Regenerative Medicine

Background:

• Mammalian lung removal (pneumonectomy) triggers compensatory growth of the remaining lung, including increased alveoli.
• The precise mechanisms of compensatory neoalveolarization remain incompletely understood.
• Alpha-smooth muscle actin (SMA) is a marker for myofibroblasts, crucial in tissue repair and growth.

Purpose of the Study:

• To investigate the role of myofibroblasts and SMA expression in compensatory lung growth after pneumonectomy.
• To identify the cellular sources and functional characteristics of SMA-expressing cells in lung regeneration.

Main Methods:

• Induction of SMA expression in the pleura and subpleural regions following pneumonectomy in a mammalian model.
• Assessment of SMA induction dependency on pleural stretch using plombage and phrenic nerve transection.
• Laser microdissection of regenerating alveolar ducts for single-cell gene expression analysis via microfluidic quantitative PCR.

Main Results:

• Pneumonectomy induced SMA expression in pleural cells, dependent on pleural deformation (stretch).
• A significant increase in SMA-positive (SMA+) cells was observed in subpleural alveolar ducts within 3 days.
• Single-cell analysis revealed that Acta2+ (SMA+) cells exhibit heightened transcriptional activity, including TGF signaling and repair-related genes, compared to other cell types.

Conclusions:

• Myofibroblast-like cells expressing SMA are activated in the pleura and subpleural lung regions post-pneumonectomy.
• Pleural stretch is a key mechanical stimulus for SMA induction and subsequent compensatory lung growth.
• These SMA+ myofibroblast-like cells play a significant role in the regenerative process of compensatory lung growth.