Related Experiment Video
Updated: Jul 11, 2025
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
PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosis via the JNK/P53 signaling pathway
Chanyuan Lv1, Liuyi Zhou1, Yongkang Meng1
1Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; JiNan Key Laboratory of Cardiovascular Disease, Shandong 250021, China.
Insights
Protein kinase D (PKD) knockdown reduces cardiac hypertrophy and ferroptosis by inhibiting the JNK/P53 pathway. This finding offers new insights into treating heart failure and cardiovascular adverse events.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Cellular Metabolism
Background:
- Cardiac hypertrophy is linked to energy metabolism, autophagy, and ferroptosis, contributing to heart failure.
- Protein kinase D (PKD) plays a detrimental role in cardiac hypertrophy, but its connection to ferroptosis is not well understood.
Purpose of the Study:
- To investigate the role of ferroptosis in Protein Kinase D (PKD)-mediated cardiac hypertrophy.
- To elucidate the involvement of the Jun N-terminal kinase (JNK)/P53 signaling pathway in this process.
Main Methods:
- A cardiac hypertrophy model was induced using angiotensin II (Ang II) in mice.
- Adeno-associated virus serotype 9 (AAV9) was used for PKD knockdown or control.
- Echocardiography, cardiomyocyte morphology, ferroptosis markers, and JNK/P53 pathway proteins were analyzed.
Main Results:
- PKD knockdown significantly reduced Ang II-induced cardiac hypertrophy and improved cardiac function.
- Inhibition of ferroptosis was observed following PKD knockdown.
- The JNK/P53 signaling pathway was confirmed to be involved in these effects both in vivo and in vitro.
Conclusions:
- PKD knockdown mitigates cardiac hypertrophy and ferroptosis.
- The JNK/P53 signaling pathway is a key mediator in PKD-associated cardiac hypertrophy and ferroptosis.
Background:
Cardiac hypertrophy is studied in relation to energy metabolism, autophagy, and ferroptosis, which are associated with cardiovascular adverse events and chronic heart failure. Protein kinase D (PKD) has been shown to play a degenerative role in cardiac hypertrophy. However, the role of ferroptosis in PKD-involved cardiac hypertrophy remains unclear.
Methods:
A cardiac hypertrophy model was induced by a subcutaneous injection of angiotensin II (Ang II) for 4 weeks. Adeno-associated virus serotype 9 (AAV9)-PKD or AAV9-Negative control were injected through the caudal vein 2 weeks prior to the injection of Ang II. The degree of cardiac hypertrophy was assessed using echocardiography and by observing cardiomyocyte morphology. Levels of ferroptosis and protein expression in the Jun N-terminal kinase (JNK)/P53 signaling pathway were measured both in vivo and in vitro.
Results:
The results indicated that PKD knockdown reduces Ang II-induced cardiac hypertrophy, enhances cardiac function and inhibits ferroptosis. The involvement of the JNK/P53 pathway in this process was further confirmed by in vivo and in vitro experiments.
Conclusion:
In conclusion, our findings suggest that PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosis via the JNK/P53 signaling pathway.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:22PI3K/mTOR/AKT Signaling Pathway
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System