| First Author | Sun X | Year | 2019 |
| Journal | Cell Signal | Volume | 62 |
| Pages | 109331 | PubMed ID | 31154001 |
| Mgi Jnum | J:295746 | Mgi Id | MGI:6453496 |
| Doi | 10.1016/j.cellsig.2019.05.016 | Citation | Sun X, et al. (2019) Inhibition of 4E-BP1 phosphorylation promotes tubular cell escaping from G2/M arrest and ameliorates kidney fibrosis. Cell Signal 62:109331 |
| abstractText | Upon occurrence of kidney injury, tubular cells arrested in G2/M stage may promote interstitial fibroblast activation and kidney fibrosis through producing large amounts of pro-fibrotic cytokines. MTORC1 signaling is essential for controlling cell growth, however, the role and mechanisms for mTORC1 in regulating tubular cell cycle progression during kidney fibrosis are not clear. Here we reported that p-S6 abundance was increased at 15min, reached peak at 1h and declined from 3h to 24h, while the abundance of p-4E-BP1 and p-Histone H3 was increased from 15min to 24h in tubular epithelial cells at the similar pattern after serum stimulation. The phosphorylation of 4E-BP1 was prohibited in NRK-52E cells by the transfection of 4E-BP1 plasmid with four phospho-sites mutation (4E-BP1A4). 4E-BP1A4 transfection led to less G2/M cell arrest as well as the production of pro-fibrotic cytokine and extracellular matrix in NRK-52E cells. In addition, aristolochic acid (AA)-induced tubular cell G2/M arrest induced by treatment was also largely attenuated in NRK-52E cells transfected with 4E-BP1A4. In mouse kidneys with UUO nephropathy, p-4E-BP1 abundance was markedly elevated in the mitotic tubular cells. Therefore, these data indicates that suppressing 4E-BP1 phosphorylation may inhibit tubular cell G2/M-arrest and kidney fibrosis. |
