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07:55
Isolation of Lung Retinoid-Containing Cells by Cell Sorting
Published on: April 11, 2025
184
Cortisol regulates neonatal lung development via Smoothened.
Shanshan Lu1, Yifei Chen1, Jiawen Song2
1The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
Respiratory Research
|January 18, 2025
Summary
Cortisol, a steroid, prevents neonatal respiratory distress by blocking fibroblast proliferation via the Sonic Hedgehog pathway. This competitive binding to SMO is crucial for normal lung development and maturation in newborns.
Area of Science:
- Neonatal medicine
- Molecular biology
- Developmental biology
Background:
- Neonatal respiratory distress syndrome (NRDS) is a leading cause of infant mortality.
- Corticosteroids are used to prevent NRDS, but their mechanism is unclear.
Purpose of the Study:
- To investigate the direct binding of cortisol to Smoothened (SMO).
- To explore cortisol's effect on the Sonic Hedgehog (SHH) pathway in neonatal lung development.
Main Methods:
- Molecular docking simulations and in vitro binding assays.
- CRISPR-Cas9 gene editing to create a SMO mutant mouse model (Smoa/a).
- Morphological analysis, single-cell RNA sequencing, and FISH on lung tissues.
Main Results:
- Cortisol inhibits SHH/SMO-mediated lung fibroblast proliferation.
- Cortisol competitively binds to SMO's cysteine-rich domain (CRD), blocking cholesterol binding and signaling activation.
- Smoa/a mice showed immature lungs with fibroblast over-proliferation and reduced surfactant protein.
Conclusions:
- Cortisol regulates neonatal lung maturation by competitively binding to SMO's CRD.
- This mechanism involves modulating cholesterol's stimulation of SMO and the SHH pathway.
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