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Lipopolysaccharide induces filtrate leakage from renal tubular lumina into the interstitial space via a proximal tubular Toll-like receptor 4–dependent pathway and limits sensitivity to fluid therapy in mice by Nakano, Daisuke; Kitada, Kento; Wan, Ningning; Zhang, Yahua; Wiig, Helge; Wararat, Kittikulsuth; Yanagita, Motoko; Lee, Syann; Jia, Lin; Titze, Jens M.; Nishiyama, Akira is a Medicine article available to read on EtoBox.

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Sustained oliguria during fluid resuscitation represents a perplexing problem in patients undergoing therapy for septic acute kidney injury. Here, we tested whether lipopolysaccharide induces filtrate leakage from the proximal tubular lumen into the interstitium, thus disturbing the recovery of urine output during therapy, such as fluid resuscitation, aiming to restore the glomerular filtration rate. Intravital imaging of the tubular flow rate in the proximal tubules in mice showed that lipopolysaccharide did not change the inflow rate of proximal tubule filtrate, reflecting an unchanged glomerular filtration rate, but significantly reduced the outflow rate, resulting in oliguria. Lipopolysaccharide disrupted tight junctions in proximal tubules and induced both paracellular leakage of filtered molecules and interstitial accumulation of extracellular fluid. These changes were diminished by conditional knockout of Toll-like receptor 4 in the proximal tubules. Importantly, these conditional knockout mice showed increased sensitivity to fluid resuscitation and attenuated acute kidney injury. Thus, lipopolysaccharide induced paracellular leakage of filtrate into the interstitium via a T

Who reads Lipopolysaccharide induces filtrate leakage from renal tubular lumina into the interstitial space via a proximal tubular Toll-like receptor 4–dependent pathway and limits sensitivity to fluid therapy in mice?

Author

Nakano, Daisuke; Kitada, Kento; Wan, Ningning; Zhang, Yahua; Wiig, Helge; Wararat, Kittikulsuth; Yanagita, Motoko; Lee, Syann; Jia, Lin; Titze, Jens M.; Nishiyama, Akira

Publisher

Nature Publishing Group; Elsevier ; Elsevier Inc.; Elsevier BV; ScienceOpen (ISSN 0085-2538)

Published

2020

Language

EN

Field

Medicine (Health Sciences)