| First Author | Liu J | Year | 2016 |
| Journal | Cell Death Dis | Volume | 7 |
| Pages | e2183 | PubMed ID | 27054338 |
| Mgi Jnum | J:315459 | Mgi Id | MGI:6830482 |
| Doi | 10.1038/cddis.2016.89 | Citation | Liu J, et al. (2016) beta-Arrestins promote podocyte injury by inhibition of autophagy in diabetic nephropathy. Cell Death Dis 7:e2183 |
| abstractText | beta-Arrestins are multifunctional proteins originally identified as negative adaptors of G protein-coupled receptors (GPCRs). Emerging evidence has also indicated that beta-arrestins can activate signaling pathways independent of GPCR activation. This study was to elucidate the role of beta-arrestins in diabetic nephropathy (DN) and hypothesized that beta-arrestins contribute to diabetic renal injury by mediating podocyte autophagic process. We first found that both beta-arrestin-1 and beta-arrestin-2 were upregulated in the kidney from streptozotocin-induced diabetic mice, diabetic db/db mice and kidney biopsies from diabetic patients. We further revealed that either beta-arrestin-1 or beta-arrestin-2 deficiency (Arrb1(-/-) or Arrb2(-/-)) ameliorated renal injury in diabetic mice. In vitro, we observed that podocytes increased both beta-arrestin-1 and beta-arrestin-2 expression levels under hyperglycemia condition and further demonstrated that beta-arrestin-1 and beta-arrestin-2 shared common mechanisms to suppress podocyte autophagy by negative regulation of ATG12-ATG5 conjugation. Collectively, this study for the first time demonstrates that beta-arrestin-1 and beta-arrestin-2 mediate podocyte autophagic activity, indicating that beta-arrestins are critical components of signal transduction pathways that link renal injury to reduce autophagy in DN. Modulation of these pathways may be an innovative therapeutic strategy for treating patients with DN. |
