The role of the transcription factor Miz1 in asthma

  • Liu, Jing (PD/PI)

Project: Research project

Project Details

Description

In this proposal, we will study a novel molecular mechanism by which the transcription factor Miz1 controls the allergic response during asthma thereby identifying potential therapeutic targets for prevention and treatment of asthma.

Overwhelming evidence shows that Toll-like receptor 4 (TLR4)-mediated inflammatory response in airway epithelial cells (ECs) plays a central role in the development of allergy to a variety of environmental allergens. Recently, we uncovered that the transcription factor Miz1 is required for modulating lipopolysaccharide (LPS)-induced, TLR4-mediated inflammation in lung epithelial cells. Loss of the transcriptional repression activity of Miz1 in lung ECs results in hyper-inflammation in intratracheal LPS-treated mice, through transcriptional repression of C/EBP, an amplifier of LPS-induced inflammation. More importantly, loss of the transcriptional activity of Miz1 promotes airway inflammation in a murine model of asthma induced by house dust mites (HDM). In this proposal, we propose the studies to test whether Miz1 plays a critical role in regulation of the allergic response during asthma.

This proposal is novel, as it will study how Miz1 controls the allergic sensitization during asthma and how Miz1 itself is regulated during the pathogenesis of asthma. These studies will put forward a novel paradigm regarding the molecular mechanism underlying the allergic sensitization during asthma, which has significant clinical implications.
StatusFinished
Effective start/end date7/1/136/30/16

Funding

  • American Asthma Foundation (13-0114)

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