Decreases in Podocin, CD2-Associated Protein (CD2AP) and Tensin2 May Be Involved in Abuminuria during Septic Acute Renal Failure

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概要

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• Podocytes have a peculiar structure constituting slit diaphragm (SD) and foot process (FP), and plays essential roles in the glomerular filtration barrier. There is now ample evidence that SD- and FP-associated molecules, such as podocin and CD2-associated protein (CD2AP), are down-regulated during albuminuria of chronic kidney disease. However, it is still unclear whether these molecules are altered during acute renal failure (ARF) with albuminuria. Using lipopolysaccharide (LPS)-treated mice as a model of septic ARF, we provide evidence that the expression of SD- and FP-associated molecules becomes faint, along with albuminuria. In the LPS-treated mice, urinary albumin levels gradually increased, associated with the elevation of blood urea nitrogen levels, indicating the successful induction of albuminuria during septic ARF. In this pathological process, glomerular podocin expression became faint, especially at 36 hr post-LPS challenge (i.e., a peak of albuminuria). Likewise, LPS treatment led to a significant decrease in CD2AP, an anchorage between podocin and F-actin. With regard to this, tensin2 is a novel molecule that stabilizes F-actin extension. Interestingly, glomerular tensin2 expression levels were also decreased during the albuminuric phase, associated with losses of glomerular F-actin and synaptopodin under septic states. As a result, there were some lesions of podocytic FP effacement, as shown by electron microscopy. Based on these data, we emphasize the importance of concomitant decreases in podocin, CD2AP and tensin2 during septic ARF-associated proteinuria.

著者

• KATO TAKASHI

  Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental

• Mizuno Shinya

  Division Of Molecular Regenerative Medicine Course Of Advanced Medicine Osaka University Graduate Sc

• MIZUNO-HORIKAWA Yoko

  Protein Research Institute, Osaka University

• MIZUNO Shinya

  Division of Molecular Regenerative Medicine, Department of Biochemistry and Molecular Biology, Osaka University Graduate School of Medicine

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