LncRNA Interacts With STAT6 Upon IL13/IL4 Activation In Asthma Inflammation

Abstract

Long non-coding RNAs (lncRNAs), have been implicated in inflammation, cancer and autoimmune diseases. They interact with epithelial cells in the lungs and impact inflammatory response elicited by cytokines IL-13/IL-4 (interleukins 13 and 4) through the JAK/STAT (Janus kinase/signal transducer and activation of transcription) signaling pathway however, little is known about the impact of lncRNAs in asthma inflammatory responses. Airway epithelial cells deficient in some specific lncRNAs in literature have been discovered to express increased STAT signaling following IL-13 stimulation therefore we hypothesize a direct interaction of some RNAs with STAT6 upon binding to DNA during IL-13/STAT6 activation. Critical to type 2 asthma inflammatory responses initiated by IL-13/IL-4 stimulation in bronchial cells is STAT6 which causes cellular differentiation, hyperplasia, and mucin production in concert with airway remodeling. Discovering more about the signal transducer will improve current knowledge of pathophysiology of this subset of asthma. Inactive STAT6 lies in the cytosol until it is phosphorylated and translocated to the nucleus where it binds DNA and activates transcription. It becomes phosphorylated and dimerizes upon IL-4/IL-13 binding to the receptor, and after that STAT6 signaling cascade evolves to activate downstream genes by binding DNA with other protein complexes. Regulatory networks involve in signal transduction systems comprise RNAs that are directly involved in the expression JAK/STAT downstream genes during inflammatory responses. Until now it has not been discovered how 1L-13 initiates differentiation upon activation of STAT6 hence discovering other interactomes upon STAT6 binding DNA is paramount. We intend to use proximal protein interaction mechanisms to identify critical players in STAT6 transcription activation and then use mass spectrometry to identify the interacting biomolecules and the state of interaction and then determine how the loss of these biomolecules impacts STAT6 activation using ChIP-Seq.