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SPLUNC1 protein

Question
Hello
Could you give some information concerning SPLUNC1 and its effects in cystic fibrosis? Do we know well this protein or is it only the beginning of the research? Are there studies planned ?
Thanks for your answer.
Answer
Hello

Research has revealed by now that in cystic fibrosis (CF) the respiratory disease is partly due to a thick, dehydrated, mucus. When CFTR works, it inhibits the sodium channel ENaC. On the opposite, in CF, when CFTR isn’t there or doesn’t work properly, ENaC absorbs sodium and water excessively in the cells, leading to the dehydration of the mucus.

There are only 4 reports in the literature concerning SPLUNC1 and CF, and 3 have been written by the same team: the team of Robert Tarran at Chapel Hill University in North Carolina, USA (references below).

They have shown in vitro (in cell cultures) that SPLUNC1 could inhibit the ENaC channel and that could lead to the rehydration of the airways’ mucus. As such, this protein could be a new therapeutic target to help make the thick mucus thinner in CF airways. However, as you can see, we are only at the beginning of the exploration of this protein and, at the moment, there is no trial planned for the patients.

Références
1: Hobbs CA, Blanchard MG, Kellenberger S, Bencharit S, Cao R, Kesimer M, Walton WG, Redinbo MR, Stutts MJ, Tarran R. Identification of SPLUNC1's ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosisairways. FASEB J. 2012 Oct;26(10):4348-59.

2: Rollins BM, Garcia-Caballero A, Stutts MJ, Tarran R. SPLUNC1 expression reduces surface levels of the epithelial sodium channel (ENaC) in Xenopus laevis oocytes. Channels (Austin). 2010 Jul-Aug;4(4):255-9. Epub 2010 Jul 4.

3: Garcia-Caballero A, Rasmussen JE, Gaillard E, Watson MJ, Olsen JC, Donaldson SH, Stutts MJ, Tarran R. SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage. Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11412-7.

4: Bingle L, Barnes FA, Cross SS, Rassl D, Wallace WA, Campos MA, Bingle CD. Differential epithelial expression of the putative innate immune molecule SPLUNC1 in cystic fibrosis. Respir Res. 2007 Nov 7;8:79.

Dr Harriet Corvol
14.11.2012