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Updated: Jun 18, 2026
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
PKC-alpha modulates TGF-beta signaling and impairs podocyte survival
Irini Tossidou1, Gabriele Starker, Janna Kruger
1Department of Medicine, Hannover Medical School, Germany.
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-beta) has been demonstrated to promote podocyte death and the development of glomerulosclerosis. In this manuscript we analyzed the role of PKC-alpha (PKCalpha) on TGF-beta1 induced apoptosis in podocytes.
Methods:
To accomplish this we generated stable murine PKCalpha deficient podocyte cell lines and examined survival- and pro-apoptotic signaling signatures as well as caspase activation after stimulation with TGF-beta.
Results:
After stimulation with TGF-beta we can demonstrate an enhanced and prolonged activation of PI3K/AKT and ERK1/2 in PKCalpha-knockout (PKCalpha-/-) podocytes compared to PKCalpha-wildtype (PKCalpha+/ +) podocytes, whereas proapoptotic signaling via p38MAPK is significantly reduced. Interestingly, activation of the Smad-pathway is also prolonged in the PKCalpha-/-podocytes. When we analyzed the underlying mechanisms we found a TGF-beta inducible interaction of PKCalpha with the TGF-beta-type-I-receptor (TGFbetaRI). Moreover, endocytosis assays showed that the TGFbetaRI is less internalized in PKCalpha-/- podocytes.
Conclusion:
Since we can demonstrate a key role for PKCalpha in the signaling response after stimulation with TGF-beta we conclude that PKCalpha might be an interesting target molecule as a "podocyte protective" therapy.
