Functions of microRNAs in lung injury and development

Abstract

Scope and Method of Study: The purpose of this study is to figure out what are the functions of microRNAs in lung development and injury. First, a microRNA microarray was set up to profile expression pattern of microRNAs in various biological processes in the lung. Lung specific microRNAs were identified using this method. Expression patterns of microRNAs in fetal lung development and alveolar epithelial cell trans-differentiation were also uncovered with this platform. The expression profiles were then verified with Northern blots and microRNA qRT-PCR. Expression of miR-127 in the fetal lung reach peak at the late stage of fetal development. Overexpression of miR-127 interrupted fetal lung morphogenesis. miR-375 is significantly decreased during alveolar epithelial cell trans-differentiation. Overexpression of miR-375 interrupted this process by inhibiting the Wnt/β-catenin signaling pathway. Expression of miR-124 is decreased during fetal lung development. miR-124 inhibits fetal alveolar epithelial cell maturation, as indicated by a decrease in surfactant protein expression and an increase in glycogen pool.

Findings and Conclusions:

1. Two miRNAs (miR-195 and miR-200c) are expressed specifically in the lung and nine miRNAs are co-expressed in the lung and another organ.

2. miR-127 has the highest expression at late stages of fetal lung development.

3. Expression of miR-127 shifts from mesenchymal cells to epithelial cells during fetal lung development.

4. miR-127 inhibits branching morphogenesis.

5. miR-375 is decreased during alveolar epithelial cell trans-differentiation.

6. The Wnt/β-catenin pathway is activated during alveolar epithelial cell transdifferentiation.

7. miR-375 reduces trans-differentiation by inhibiting the Wnt/β-catenin pathway through directly targeting FZD8.

8. miR-124 is down-regulated during fetal lung development.

9. miR-124 inhibits fetal epithelium maturation by directly targeting NFIB.