Rho-Kinase Blockade Attenuates Podocyte Apoptosis by Inhibiting the Notch Signaling Pathway in Diabetic Nephropathy
AbstractPodocyte apoptosis is a key process in the onset of diabetic nephropathy. A significant body of evidence shows that the Notch signaling pathway plays a central role in this process. We found that Rho-kinase mediates transforming growth factor β (TGF-β)-induced Notch ligand Jag1 expression. Importantly, TGF-β-mediated podocyte apoptosis was attenuated by Rho-kinase inhibition. Mechanistically, Rho-kinase regulated Jag1 induction via the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) but not Smad pathways. Consistently, the Rho-kinase inhibitor fasudil prevented albuminuria and the urinary excretion of nephrin in db/db mice and reduced the prevalence of podocyte apoptosis and Jag1 expression. Finally, the expression of Jag1 and apoptosis markers such as Bax and cyclin-dependent kinase inhibitor 1A (CDKN1A) was decreased in podocytes derived from db/db mice treated with fasudil. The present study provides evidence that Rho-kinase plays a key role in podocyte apoptosis. Rho-kinase is an attractive therapeutic target for diabetic nephropathy. View Full-Text
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Matoba, K.; Kawanami, D.; Nagai, Y.; Takeda, Y.; Akamine, T.; Ishizawa, S.; Kanazawa, Y.; Yokota, T.; Utsunomiya, K. Rho-Kinase Blockade Attenuates Podocyte Apoptosis by Inhibiting the Notch Signaling Pathway in Diabetic Nephropathy. Int. J. Mol. Sci. 2017, 18, 1795.
Matoba K, Kawanami D, Nagai Y, Takeda Y, Akamine T, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K. Rho-Kinase Blockade Attenuates Podocyte Apoptosis by Inhibiting the Notch Signaling Pathway in Diabetic Nephropathy. International Journal of Molecular Sciences. 2017; 18(8):1795.Chicago/Turabian Style
Matoba, Keiichiro; Kawanami, Daiji; Nagai, Yosuke; Takeda, Yusuke; Akamine, Tomoyo; Ishizawa, Sho; Kanazawa, Yasushi; Yokota, Tamotsu; Utsunomiya, Kazunori. 2017. "Rho-Kinase Blockade Attenuates Podocyte Apoptosis by Inhibiting the Notch Signaling Pathway in Diabetic Nephropathy." Int. J. Mol. Sci. 18, no. 8: 1795.
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