Deregulated renal magnesium transport during lipopolysaccharide-induced acute kidney injury in mice
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Magnesium (Mg2+) abnormalities during sepsis have been reported, but the underlying mechanisms during acute inflammation are poorly understood. We hypothesized that a decrease in GFR and/or changes in transporters or channels for Mg2+ could be responsible for the observed Mg2+ abnormalities. Therefore, we studied the metabolism of Mg2+ in a murine model of endotoxemia. LPS-induced hypermagnesemia was paralleled by a decrease in creatinine clearance and an increase in the fractional excretion of Mg2+. In agreement with an altered renal Mg2+ handling, endotoxemia decreased the renal expression of claudin (Cldn) 10b, Cldn16, Cldn19, parvalbumin, and of the solute carrier family (Slc) 41a3. Further, LPS increased the renal expression of Cldn14 and Slc41a1. The renal expression of the transient receptor potential melastin (Trpm) 6, Trpm7, and of cyclin M (Cnnm) 2 was unaltered in response to LPS. In vitro studies support a direct effect on the expression of Cldn10b, Cldn14, Cldn16, and Cldn19. Further, endotoxemia increased the fractional excretion of sodium, which was paralleled by a decrease of important renal sodium transporters. In the large intestine, the expression of Trpm7 was increased in response to LPS, whereas the expression of Trpm6 was decreased. Cnnm4 mRNA levels were unchanged in the large intestine. Further, Cldn12 and Na+-H+ exchanger 3 (Slc9a3) expressions were decreased in the small intestine in response to LPS. Our findings indicate that endotoxemia is associated with hypermagnesemia and a disturbed Mg2+ handling. It seems likely that LPS-induced hypermagnesemia is due to the decrease in renal function in response to LPS.
KeywordsInflammation Endotoxemia Claudin Sepsis Renal function Magnesium Intestine
The technical assistance provided by Ramona Mogge and Andrea Agli is gratefully acknowledged.
This study was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG, SFB699/B5).
Compliance with ethical standards
All animal experiments were conducted according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the local animal protection committee.
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