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Skin tight: macrophage-specific COX-2 induction links salt handling in kidney and skin
Johannes Stegbauer, Thomas M. Coffman
Johannes Stegbauer, Thomas M. Coffman
Published October 20, 2015
Citation Information: J Clin Invest. 2015;125(11):4008-4010. https://doi.org/10.1172/JCI84753.
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Commentary

Skin tight: macrophage-specific COX-2 induction links salt handling in kidney and skin

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Abstract

The relationship between dietary salt intake and the associated risk of hypertension and cardiovascular disease is an important public health concern. In this issue of the JCI, a study by Zhang and associates shows that consumption of a high-sodium diet induces expression of cyclooxygenase-2 (COX-2) in macrophages, resulting in enhanced levels of prostaglandin E2 (PGE2), autocrine activation of the macrophage E-prostanoid 4 (EP4) receptor, and subsequent triggering of parallel pathways in the kidney and in skin that help dispose of excess sodium. The authors found that blockade or genetic elimination of the COX-2/PGE2/EP4 receptor pathway in hematopoietic cells causes salt-sensitive hypertension in mice. These studies illuminate an unexpected central role for the macrophage in coordinating homeostatic responses to dietary salt intake and suggest a complex pathophysiology for hypertension associated with NSAID use.

Authors

Johannes Stegbauer, Thomas M. Coffman

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Figure 1

The COX-2/mPGES-1/EP4 receptor pathway in macrophages maintains sodium homeostasis by influencing salt secretion in the kidney and extrarenal sodium storage.

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The COX-2/mPGES-1/EP4 receptor pathway in macrophages maintains sodium h...
In this issue, Zhang and colleagues demonstrate that a high-salt diet induces expression of COX-2, thereby enhancing PGE2 production and autocrine EP4 receptor (EP4R) signaling. In mice lacking the COX-2/mPGES-1/EP4 receptor pathway in hematopoietic cells, extrarenal salt storage and sodium secretion by the kidney are dysfunctional, resulting in the development of hypertension.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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