Gap junctional intercellular communication of renal podocytes

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Podocyte injury or podocyte loss in the renal glomerulus has been proposed as the crucial mechanism in the development of focal segmental glomerulosclerosis. However, it is poorly understood how podocytes respond to injury. In this study, glomerular expression of connexin43(Cx43) gap junction protein was examined at both protein and transcript levels in an experimental model of podocyte injury, puromycin aminonucleoside(PAN) nephrosis. Inmunofluorescence and immunoelectron microscopy showed a striking increase in signals for Cx43 of podocytes in the early to nephritic stage of PAN nephrosis. Consistently, Western blotting and ribonuclease protection assay revealed a distinct increase of Cx43 protein, phosphorylation and transcript in glomeruli during PAN nephrosis. A single-cell microinjection of fluorescent dye, Lucifer yellow, into cultured podocytes demonstrated the presence of functional gap junctional intercellular communication(GJIG) in podocytes. Immunofluorescence microscopy using fetal kidney showed that expression of Cx43 in podocytes increased in parallel with podocyte differentiation. Gap junction formation needs the other supporting junction such as adherens junction. However, we could not find classic cadherins or catenins in podocytes in PAN nephrosis. Instead, coxsackievirus and adenovirus receptor(CAR) was detected in podocytes. CAR is an integral membrane component of tight junction and promotes homotypic cell aggregation. Gap junction is located closely to tight junction in podocytes.Thus, it is concluded that Cx43-mediated GJIC is present between podocytes, suggesting that podocytes may respond to injury as an integrated epithelium on a glomerulus rather than individually as a separate cell.