PKC-alpha modulates TGF-β signaling and impairs podocyte survival
Tossidou I, Starker G, Krueger J, Meier M, Leitges M, Hallerand H, Schiffer M (2009)
Publication Type: Journal article
Publication year: 2009
Journal
Book Volume: 24
Pages Range: 627-634
Journal Issue: 5-6
DOI: 10.1159/000257518
Abstract
Background: Progressive loss of podocytes has been documented as an early lesion in the development of glomerular disease. In a variety of glomerular diseases, including diabetic nephropathy the activation of transforming growth factor-beta (TGF-β) has been demonstrated to promote podocyte death and the development of glomerulosclerosis. In this manuscript we analyzed the role of PKC-alpha (PKCα) on TGF-β1 induced apoptosis in podocytes. Methods: To accomplish this we generated stable murine PKCα deficient podocyte cell lines and examined survival-and pro-apoptotic signaling signatures as well as caspase activation after stimulation with TGF-β. Results: After stimulation with TGF-β we can demonstrate an enhanced and prolonged activation of PI3K/AKT and ERK1/2 in PKCα-knockout (PKCα-/-) podocytes compared to PKCα-wildtype (PKCα+/ +) podocytes, whereas proapoptotic signaling via p38MAPK is significantly reduced. Interestingly, activation of the Smad-pathway is also prolonged in the PKCα-/-podocytes. When we analyzed the underlying mechanisms we found a TGF-β inducible interaction of PKCα with the TGF-β-type-I-receptor (TGFβRI). Moreover, endocytosis assays showed that the TGFβRI is less internalized in PKCα-/-podocytes. Conclusion: Since we can demonstrate a key role for PKCα in the signaling response after stimulation with TGF-β we conclude that PKCα might be an interesting target molecule as a "podocyte protective" therapy. Copyright © 2009 S. Karger AG, Basel.
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APA:
Tossidou, I., Starker, G., Krueger, J., Meier, M., Leitges, M., Hallerand, H., & Schiffer, M. (2009). PKC-alpha modulates TGF-β signaling and impairs podocyte survival. Cellular Physiology and Biochemistry, 24(5-6), 627-634. https://doi.org/10.1159/000257518
MLA:
Tossidou, Irini, et al. "PKC-alpha modulates TGF-β signaling and impairs podocyte survival." Cellular Physiology and Biochemistry 24.5-6 (2009): 627-634.
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