AI Article Synopsis
- The study investigates how the protein PKC-alpha (PKCalpha) affects podocyte cell survival when stimulated by TGF-beta, a factor involved in glomerular diseases.
- Researchers created podocyte cell lines lacking PKCalpha to analyze changes in cell survival and apoptosis signaling, observing distinct differences in signaling pathways compared to normal cells.
- The findings suggest that PKCalpha plays a crucial role in modulating the cell's response to TGF-beta, indicating that targeting PKCalpha could be a promising approach for protecting podocytes from damage in kidney diseases.
Article 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-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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1159/000257518 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!