| First Author | Gao P | Year | 2014 |
| Journal | Biochim Biophys Acta | Volume | 1839 |
| Issue | 11 | Pages | 1110-20 |
| PubMed ID | 25046864 | Mgi Jnum | J:218484 |
| Mgi Id | MGI:5617668 | Doi | 10.1016/j.bbagrm.2014.06.018 |
| Citation | Gao P, et al. (2014) Nrf2 ameliorates diabetic nephropathy progression by transcriptional repression of TGFbeta1 through interactions with c-Jun and SP1. Biochim Biophys Acta 1839(11):1110-20 |
| abstractText | Diabetic nephropathy (DN) is one of the major complications in diabetes patients. Reactive oxygen species (ROS) play key roles in DN progression. As a primary transcription factor, Nrf2 controls the antioxidant response to maintain cellular redox homeostasis. Herein we systemically examined the role of Nrf2 in DN progression and its regulatory mechanism in a mouse model bearing type II diabetes and in cultured human renal mesangial cells (HRMCs). We found that Nrf2 could ameliorate DN progression by transcriptional repression of TGFbeta1 in vivo and in vitro. Moreover, Nrf2 bound to the specific region in TGFbeta1 promoter by interactions with transcription factors c-Jun and SP1. Significant abolishment of Nrf2-mediated TGFbeta1 transcriptional repression could be accomplished by knockdown of either c-Jun or SP1, and site-directed mutagenesis of c-Jun and SP1 binding sites in the TGFbeta1 promoter specific region. Moreover, after interacting with c-Jun and SP1, Nrf2 inhibited c-Jun and SP1 activations, and thus reversed c-Jun- and SP1-promoted TGFbeta1 transcription. In all, Nrf2 could slow down DN progression by repression of TGFbeta1 in a c-Jun and SP1-dependent way. Our findings may provide novel clues for DN preventions and interventions in clinic. |
