Ramachandran, Shyam

MicroRNAs comprise a class of small non-coding RNAs ranging from 18-25nt long. They are produced naturally in plant and animal species and have been attributed with post-transcriptional silencing properties. Over half of all eukaryotic genes are microRNA-regulated, with a single microRNA capable of regulating the expression of 2 to 300 genes. Changes in their expression pattern are known to affect a variety of biological processes including cell cycle checkpoint, DNA repair, senescence, organogenesis, innate immunity, etc. Cystic fibrosis (CF) is an inherited genetic disease with an autosomal-recessive inheritance pattern. It is caused by mutations in a single gene called the cystic fibrosis transmembrane conductance regulator (CFTR). In CF, the lungs are particularly susceptible to infection, with concomitant inflammation and alteration in airway morphology. Of these, airway inflammation is widely recognized as a major factor in the pathogenesis of CF lung disease. A characteristic feature of this phenotype is the influx of polymorphonuclear neutrophils (PMN) into the airways and the resultant damage to lung tissue caused by the release of mediators such as reactive oxygen species and proteolytic enzymes. A plethora of mechanisms have been explored over the past two decades to explain the increased susceptibility of CF lungs to pulmonary infection and the resultant damage. It is widely believed that the disease pathology of CF is a result of the complex interplay between innate immunity, infection and inflammation at the epithelial surface due to the genetic defect in anion transport. We hypothesize that the loss of CFTR initiates events that alter the cellular microRNA expression profile of cells, thereby contributing to the complex pathology seen in CF patients.