They identified a key mechanism for human lung development – News

IGFBP3 is a molecule widely studied in both pathological processes such as cancer and physiological processes and is involved in the regulation of cell proliferation, differentiation and survival. In the new study, they revealed a hitherto unknown aspect: the importance of this protein during human lung embryogenesis. ​​​​
As Melissa Acosta-Plasencia, a UB researcher and first author of the paper along with fellow researcher Joan J. Castellano, explains, “This protein helps keep lung epithelial cells—those that line the inside of the lungs—healthy.” “undifferentiated”, that is, it allows them to retain the ability to turn into different types of cells.

Subsequently, as the lungs develop, IGFBP3 expression must decrease in order for cell differentiation to occur, a process required for proper formation of lung tissue. “As embryogenesis progresses, this protein needs to be silenced, which tells us that it is key to the maintenance of lung stem cells,” the researcher adds.

The study also describes the interaction between IGFBP3 and miR-34a, a microRNA-type molecule that plays a critical role in the control of gene expression. Beginning at week 8 of lung development, this molecule acts by inhibiting the production of IGFBP3 in the lung mesenchyme and subsequently in the epithelium, promoting the cellular differentiation required during this phase of the developmental process.

Modeling lung development using organoids

The work was carried out through the creation and creation of organoids obtained from embryonic lungs during the period from 8 to 12 weeks of human development, which reproduce this organ at the molecular and cellular level. “In our study, we observed that gene expression IGFBP3 It was associated with embryonic lung progenitor cells. That’s why we needed a model in vitro who could reproduce this expression,” the researcher emphasizes.
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Organoids based on pluripotent stem cells reproduce in 3D a specific tissue, in this case the lining of the lungs, with which they can interact at different levels. “In this way, we were able to activate cell differentiation processes and silence certain genes in order to evaluate their effect on lung development,” he elaborates.