Podocytes have a peculiar structure constituting slit diaphragm (SD) and foot process (FP), and play 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.