| First Author | Lv Z | Year | 2018 |
| Journal | Cell Death Dis | Volume | 9 |
| Issue | 3 | Pages | 342 |
| PubMed ID | 29497040 | Mgi Jnum | J:282133 |
| Mgi Id | MGI:6358979 | Doi | 10.1038/s41419-018-0353-z |
| Citation | Lv Z, et al. (2018) Podocyte-specific Rac1 deficiency ameliorates podocyte damage and proteinuria in STZ-induced diabetic nephropathy in mice. Cell Death Dis 9(3):342 |
| abstractText | Activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) has been implicated in diverse kidney diseases, yet its in vivo significance in diabetic nephropathy (DN) is largely unknown. In the present study, we demonstrated a podocyte-specific Rac1-deficient mouse strain and showed that specific inhibition of Rac1 was able to attenuate diabetic podocyte injury and proteinuria by the blockade of Rac1/PAK1/p38/beta-catenin signaling cascade, which reinstated the integrity of podocyte slit diaphragms (SD), rectified the effacement of foot processes (FPs), and prevented the dedifferentiation of podocytes. In vitro, we showed Rac1/PAK1 physically bound to beta-catenin and had a direct phosphorylation modification on its C-terminal Ser675, leading to less ubiquitylated beta-catenin, namely more stabilized beta-catenin, and its nuclear migration under high-glucose conditions; further, p38 activation might be responsible for beta-catenin nuclear accumulation via potentiating myocyte-specific enhancer factor 2C (MEF2c) phosphorylation. These findings provided evidence for a potential renoprotective and therapeutic strategy of cell-specific Rac1 deficiency for DN and other proteinuric diseases. |
