Budding Uninhibited by Benzimidazole-1 Insufficiency Prevents Acute Renal Failure in Severe Sepsis by Maintaining Anticoagulant Functions of Vascular Endothelial Cells

Abstract

Severe sepsis is critical to health and can result in acute renal failure (ARF). Tissue factor (TF) and thrombomodulin (TM) play key roles in vascular endothelial functions by helping maintain microcirculation in the kidney. Budding uninhibited by benzimidazole-1 (Bub1) plays a role in Akt and JNK signaling, which control TF and TM, respectively. We hypothesized that Bub1 could control vascular endothelial function in sepsis. The aim of this study was to determine the role of Bub1 in septic ARF. We used Mouse cecum ligation and puncture (CLP) using low Bub1 expressing (Bub1) and wild-type (Bub1) mice in vivo and lipopolysaccharide (LPS) stimulation of human aortic endothelial cell (HAEC) in vitro. Bub1 mice had a higher survival rate after CLP than Bub1. Bub1 mice had more severe ARF after CLP than Bub1 with blood biochemical and pathological analyses. TF expression in Bub1 mice and control HAEC (control) significantly increased in the septic model compared with Bub1 and Bub1 silenced HAEC (siBub1). TM expression in the control significantly decreased after LPS stimulation compared with siBub1. Akt and JNK phosphorylation of siBub1 were attenuated after LPS stimulation. Associations of Bub1 with Akt or JNK after LPS stimulation of HAEC were detected using immunoprecipitation, suggesting that Bub1 is involved in the phosphorylation of Akt and JNK after LPS stimulation. Bub1 insufficiency attenuates TF expression and reduces TM suppression by blocking Akt and JNK phosphorylation, respectively, thus leading to the prevention of ARF and death caused by sepsis.

Comprehensive analysis reveals a four-gene signature in colorectal cancer

“…What’s more, it was reported that AURKA has associated with CRC liver metastasis (CRLCM) ( 26 , 27 ). Budding uninhibited by benzimidazoles ( BUB1 ) is also a member of the serine/threonine-protein kinase family ( 28 ). Over 90 percentages of all human solid tumors have a common feature that mutations occur in the spindle checkpoints ( 29 ).…”

Role of Programmed Cell Death 4 (PDCD4)-Mediated Akt Signaling Pathway in Vascular Endothelial Cell Injury Caused by Lower-Extremity Ischemia-Reperfusion in Rats

“…However, under pathological conditions, the CEC count can rise markedly [24]. TM and vWF are also key markers used in monitoring endothelial injury [25–27]. Wu et al reported that miR-26a can inhibit PFKFB3 in a targeted manner, thereby reducing VEC injury caused by lower-extremity ischemia-reperfusion.…”

Evaluation of different commercial antibodies for their ability to detect human and mouse tissue factor by western blotting

“…We found 29 papers that used this antibody to measure human, mouse, rabbit and canine TF by a variety of methods, including 15 that used the antibody for western blotting (Table S1). 33‐61 Importantly, Abcam evaluated the ability of the antibody to detect human TF in wild‐type and KO cell lines by western blotting 62 . Based on the data they obtained, they recently withdrew ab151748 and stated that “after evaluation, using a HAP1 knockout cell line, ab151748 was not shown to react specifically with the target protein and has therefore been discontinued.” We confirmed that this antibody does not detect mouse TF by western blotting but rather a nonspecific band.…”