Project name: Project category: Kind of research: Country: Principle investigator:

Implication of miRNA in CF lung pathology: Studies of inflammation and ANO1 regulation by miRNAs

France Olivier Tabary
Status: Ongoing

Cystic fibrosis (CF) is an autosomal recessive disorder due to mutations in the CF transmembrane conductance regulator (CFTR) gene. These mutations cause impaired airway epithelial cell CFTR channels, loss of airway surface liquid, reduced mucus clearance, recurrent infection and chronic inflammation.

Despite the prominent role of inflammation in a wide range of diseases, little is known about its regulation and influence on the human lung epithelial cell. We well known that NFkB and MAP kinases pathway are involved but the origin of this induction remain unknown.
More, in a previous study partky funded by Vaincre La Mucoviscidose, we have demonstrated that ANO1/TMEM16a calcium chloride channel is downregulated in CF. The origin of this regulation is also unclear. It is recognized that small non-coding RNAs (microRNAs) (gene/protein regulators) could be differentially expressed in CF. If this is the case the pattern of expression of different proteins in the cell may be changed. We will assess if microRNAs upregulated in CF influence production of some candidate genes.

So, we proposed to analyse one aspect of epigenetic to regulate proteins by miRNA analysis.

The aims of this study is to analyse:
1. Potential miRNA in the regulation of some candidate protein (ANO1/TMEM16a and some inflammatory poteins),
2. All miRNA deregulated in CF context, and
3. The effects of drugs (Azithromycin, Vertex compounds…) on miRNA expression.

This study will help to define the regulation and complex biology of some genes/proteins and in airway epithelium of patients with CF. This project will be an extensive miRNA study in the context of CF.

Project amount (€): 50.000

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