MicroRNA-132 regulates salt-dependent steady-state renin levels in mice
Open Access
- 14 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Communications Biology
- Vol. 3 (1), 1-11
- https://doi.org/10.1038/s42003-020-0967-4
Abstract
The body's salt and fluid balance is regulated by the renin-angiotensin-aldosterone system. Generation of prostaglandin-E2 (PGE2) in a cyclo-oxygenase-2 (COX-2)-dependent manner in the macula densa, the salt-sensing cells of the kidney, plays a dominant role in renin regulation. Here we show that miR-132 directly targets Cox-2 and affects subsequent PGE2 and renin levels. MiR-132 is induced and reduced by low- and high salt treatment, respectively, in a p38- and ERK1/2-independent and CREB- and salt inducible kinase-dependent manner. Silencing of miR-132 in mice increases macula densa COX-2 expression and elevates PGE2 and renin levels, which are abrogated by the selective COX-2-inhibitor Celecoxib. Furthermore, a low or high salt diet induces and reduces macula densa miR-132 expression, while low salt diet combined with silencing miR-132 further increases renin levels. Taken together, we demonstrate a posttranscriptional regulatory role for salt-dependent miR-132 in fine-tuning the steady-state levels of renin.Funding Information
- Nierstichting (16OKG16)
- European Foundation for the Study of Diabetes
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