The decreases of heparin and nuclear WT1 in products may cause albumin-urea during the experimental sepsis in mice

Abstract

Sepsis is induced by infectious challenges, and septic organ failure often occurs under local and systemic inflammation. Albuminuria is also evident during sepsis, but little is known about the molecular basis of septic albuminuria. Using lip polysaccharide (LPS)-treated mice as a sepsis model, we found that the loss of heparin, a key component for maintaining porosity slit diaphragm, became evident in accordance with the onset of albuminuria, especially 36 h post-LPS challenge (i.e., album uric stage). Likewise, heparin mRNA levels were decreased to 13% of saline-treated mice. Such a transcriptional suppression of heparin was associated with the loss of nucleus-localized Wilma tumor-1 (WT1), a transcriptional factor for up-regulating neoprene gene. Thereafter, urinary albumin levels were decreased in mice between 72 and 96 h post-LPS challenge (i.e., recovery-stage). Notably, nuclear localization of WT1 seemed to be normalized, and neoprene mRNA and protein levels returned near the basal level 72 h post-LPS challenge. During LPS-mediated sepsis, there was a transient increase in blood interleukin-1β, a suppressor of neph-rin production in porosities. Therefore, down-regulation of neoprene by the loss in nuclear WT1, along with hyper-cytokinemia, may underlie the mechanisms by which albuminuria is induced by infectious stresses.