Identification of alveolar fibroblast subset-specific miRNA expression profiles and their impact on cell development, differentiation and subsequently alveolar septation in postnatal lung development

Introduction: It is known that the microRNAs (miRNAs) are involved in basic cell processes, coregulated by many other factors (cytokins, cell receptors, transcription factors), which all together form a sophisticated signaling networks important in maintaining tissue homeostasis and development. We aim to identify cell specific miRNA expression profiles of different lung fibroblast subpopulations, such as myofibroblast, lipofibroblast and PDGFRa- precursor cells, which are critically involved during mouse alveolar septum formation.

Methods: Based on specific gene expression of postnatal lung interstitial fibroblasts, we aim to purify them using FACS sorting, and proceed for further miRNA and mRNA microarray expression profile analysis.

Results: We expect, that fibroblast cell type-specific miRNAs exhibit temporal and spatial expression patterns, as it is assumed that lipofibroblasts, myofibroblasts and PDGFRa-precursor cells fulfill determined functions, and might transdifferentiate to each other during particular postnatal lung developmental time-points, regenerative lung growth and diseases.

Conclusion: Fibroblast subsets specified functions, stable phenotype and differentiation to might be regulated by miRNA specific profiles as a result of developmental plasticity, thus if the cells heterogeneity is kept under the control of correlated miRNA and mRNA up-/downregulation as a consequence of activation or diversification processes occurring in the cells and adaptation of particular phenotype according to physiological or pathophysiological requirements. A better understanding the processes regulating the cellular differentiation and cell fate of lung fibroblast might be helpful to develop regenerative or tissue protective therapeutic strategies of the lung.