Idiopathic Pulmonary Fibrosis (IPF) is a devastating disease of the lung that may lead to loss of normal structure/function and permanent scarring of the lung tissue. The cellular and molecular changes that lead to the development of this condition are still largely unknown. There is emerging literature showing that miRNAs play essential roles in normal development and in diseases, such as lung development and lung cancer, diabetes and heart failure. Nothing, however, is known about miRNAs in IPF. We have previously reported critical components of the microRNA machinery in the developing lungs. Our preliminary studies have identified several microRNAs selectively enriched in the embryonic and adult lung. Here we hypothesize that IPF may have cell type specific miRNA expression signatures, and that characterizing these signatures may provide the basis for the identification of disease biomarkers and therapeutic targets. We propose that miRNA signatures can be identified and further characterized by utilizing the tissues from Lung Tissue Research Consortium (LTRC) and methodologies already established in our group.
Two specific Aims are proposed for this study:
Aim 1 : to identify miRNAs significantly down- or up-regulated in lung tissue from IPF patients compared to control non-affected lungs by using miRNA microarray.
Aim 2 : to characterize the expression pattern of these miRNAs in histological sections from IPF patients and compare with control morphologically normal lungs by using in situ hybridization. Results from these studies may provide novel insights into the role of miRNAs in the pathogenesis of IPF, and help to design strategies for its diagnosis and management. (End of Abstract)
Project Narrative Idiopathic Pulmonary Fibrosis (IPF) is a devastating disease of the lung that leads to loss of normal structure/function and permanent scarring of the lung tissue. The incidence of IPF in the U.S. population is 30/100,000. Currently, the natural cause of IPF is unknown, and there are no effective treatments with a median survival of 2.8-4.2 yrs. The studying the function of miRNAs has made huge impact on several critical disease, such as lung cancer, diabetes and heart failure. Nothing, however, is known about miRNAs in IPF. We have previously reported critical components of the microRNA machinery in the developing lungs. Our preliminary studies have identified several microRNAs selectively enriched in the embryonic and adult lung. Here we hypothesize that IPF may have cell type specific miRNA expression signatures, and that characterizing these signatures may provide the basis for the identification of disease biomarkers and therapeutic targets. We propose that miRNA signatures can be identified and further characterized by using microRNA array and in situ hybridization approaches and utilizing the tissues from Lung Tissue Research Consortium (LTRC).
