Authors:	Wild, Johannes Jung, Rebecca Knopp, Tanja Efentakis, Panagiotis Benaki, Dimitra Grill, Alexandra Wegner, Joanna Molitor, Michael Garlapati, Venkata Rakova, Natalia Markó, Lajos Marton, Adriana Mikros, Emmanuel Münzel, Thomas Kossmann, Sabine Rauh, Manfred Nakano, Daisuke Kitada, Kento Luft, Friedrich Waisman, Ari Wenzel, Philip Titze, Jens Karbach, Susanne
Title:	Aestivation motifs explain hypertension and muscle mass loss in mice with psoriatic skin barrier defect
Online publication date:	12-Sep-2022
Year of first publication:	2021
Language:	english
Abstract:	Aim Recent evidence suggests that arterial hypertension could be alternatively explained as a physiological adaptation response to water shortage, termed aestivation, which relies on complex multi-organ metabolic adjustments to prevent dehydration. Here, we tested the hypothesis that chronic water loss across diseased skin leads to similar adaptive water conservation responses as observed in experimental renal failure or high salt diet. Methods We studied mice with keratinocyte-specific overexpression of IL-17A which develop severe psoriasis-like skin disease. We measured transepidermal water loss and solute and water excretion in the urine. We quantified glomerular filtration rate (GFR) by intravital microscopy, and energy and nitrogen pathways by metabolomics. We measured skin blood flow and transepidermal water loss (TEWL) in conjunction with renal resistive indices and arterial blood pressure. Results Psoriatic animals lost large amounts of water across their defective cutaneous epithelial barrier. Metabolic adaptive water conservation included mobilization of nitrogen and energy from muscle to increase organic osmolyte production, solute-driven maximal anti-diuresis at normal GFR, increased metanephrine and angiotensin 2 levels, and cutaneous vasoconstriction to limit TEWL. Heat exposure led to cutaneous vasodilation and blood pressure normalization without parallel changes in renal resistive index, albeit at the expense of further increased TEWL. Conclusion Severe cutaneous water loss predisposes psoriatic mice to lethal dehydration. In response to this dehydration stress, the mice activate aestivation-like water conservation motifs to maintain their body hydration status. The circulatory water conservation response explains their arterial hypertension. The nitrogen-dependency of the metabolic water conservation response explains their catabolic muscle wasting.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7727
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY-NC-ND
Information on rights of use:	https://creativecommons.org/licenses/by-nc-nd/4.0/
Journal:	Acta physiologica 232 1
Pages or article number:	e13628
Publisher:	Wiley-Blackwell
Publisher place:	Oxford u.a.
Issue date:	2021
ISSN:	1748-1716
Publisher DOI:	10.1111/apha.13628
Appears in collections:	JGU-Publikationen