Autocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival

摘要: Class 3 semaphorins are guidance proteins that play crucial roles during development. Semaphorins 3A (sema 3A) and 3F expressed by podocytes in vivo throughout ontogeny their function is unknown. Here we examined the expression of class (3A, 3B, 3C, 3D, 3E, 3F) receptors (neuropilins 1 2, plexins A1, A2, A3, B2, D1) undifferentiated differentiated mouse using reverse transcriptase-polymerase chain reaction (RT-PCR). All semaphorins, neuropilins 2 at similar levels. Differentiated 2–4-fold higher plexin A3 mRNA levels than podocytes. To examine semaphorin regulation, exposed to recombinant sema 3A. Sema decreased D1 ≥50% reduced A2 undetectable identify podocytes, whether regulates slit diaphragm podocyte survival. induced a dose-response podocin downregulation its interaction with CD2-associated protein nephrin, as determined Western analysis co-immunoprecipitation. evaluate role survival, quantified apoptosis caspase activity marker. 10-fold increase significantly Akt survival pathway. Our data indicate (1) immortalized culture have functional autocrine system regulated differentiation ligand availability; (2) signaling interactions slit-diaphragm decreases