Abstract P019: Upregulation of Autophagy Enhances (pro)renin Receptor Expression via P62 -erk1/2 Signaling Pathway in Podocytes
Abnormally up-regulated or down-regulated autophagy induces cell death. p62 is selectively degraded by autophagy, and was also recently reported to modulate extracellular signal-regulated kinases (ERK1/2) activity. However, the effect of autophagy on PRR expression is not known. We hypothesized that autophagy activation increases PRR expression via modulation of p62 -ERK1/2 signaling pathway. Cultured mouse podocytes were treated with the autophagy activators, rapamycin (100 nm) or Earles’s balanced salt solution (EBSS), for 48 hours. Both rapamycin and EBSS significantly increased mRNA and protein expressions of PRR (see below attached figures), decreased p62 protein levels and increased ERK1/2 activation by phosphorylating pTpY185/187. Confocal microscopy studies showed significant increase in protein levels of microtubule-associated protein-1 light chain 3B (LC3B) and PRR, and decrease of p62/SQSTM1 level in response to rapamycin or EBSS. Using autophagy related 5 (ATG5) cDNA or ATG7 cDNA transfection for 72 hours to enhance podocytes autophagy showed the same results as rapamycin and EBSS treatments. Inhibition of autophagy with bafilomycin A1 (10 nm) reversed the effects of rapamycin. ERK1/2 inhibitor U0126 (10 μM) significantly attenuated mRNA and protein expressions of PRR in podocytes treated with rapamycin, while has no effect on p62/SQSTM1 level. In conclusion, up-regulation of autophagy enhanced PRR expression through p62-ERK1/2 signaling pathway.
Author Disclosures: C. Li: None. S. Quadri: None. H. Siragy: None.
- © 2015 by American Heart Association, Inc.