Researchers of the University of Barcelona and the August Pi y Sunyer Biomedical Research Institute (IDIBAPS) have shown that the IGFBP3 protein plays a relevant role in human lung development. The results of the study, which used organoids derived from embryonic lungs, open up new perspectives on how this organ develops and lay the foundations for future strategies for both prevention and treatment of lung diseases, especially in neonatal respiratory pathologies. The study, published in the journal Stem Cell Research & Therapy , is led by Alfons Navarro, professor at the UB's Faculty of Medicine and Health Sciences and head of the IDIBAPS research group on Inflammation and Repair in Respiratory Diseases .
A key protein in the balance between pluripotency and cell differentiation
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. The new study has revealed a previously unknown aspect: the importance of this protein during human lung embryogenesis. As Melissa Acosta-Plasencia, researcher at the UB and first author of the article together with Joan J. Castellano, also a researcher, explains, "this protein helps to maintain lung epithelial cells - those that cover the inner surface of the lungs - in an undifferentiated state", that is, it allows them to maintain their capacity to develop into different cell types.
As the lung develops, IGFBP3 expression must be reduced for cell differentiation to take place, a process necessary for proper lung tissue formation. "As embryogenesis progresses, this protein needs to be silenced, which tells us that it is key to maintain lung stem cells", the researcher adds.
The study has also described the interaction between IGFBP3 and miR-34a, a microRNA-like molecule that plays a crucial role in the control of gene expression. From week 8 of lung development, this molecule acts by inhibiting IGFBP3 production in the lung mesenchyme and subsequently in the epithelium to facilitate the cell differentiation required at this stage of the development process.
Simulating lung development using organoids
The study has been carried out thanks to the generation and establishment of organoids derived from embryonic lungs between the 8th and 12th week of human development, which replicate this organ at the molecular and cellular level. "In our study, we observed that IGFBP3 gene expression was associated with embryonic lung progenitor cells. Therefore, we needed an in vitro model that could reproduce this expression", says the researcher.
The organoids, based on pluripotent stem cells, reproduce in 3D a specific tissue, in this case the lung mucosa, which can be interacted with at different levels. "Thus, we have been able to activate cell differentiation processes or silence specific genes to evaluate their effects on lung development", he explains.
