| First Author | Hemker SL | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 4 | Pages | 5782-5799 |
| PubMed ID | 32141129 | Mgi Jnum | J:294650 |
| Mgi Id | MGI:6445320 | Doi | 10.1096/fj.201902767R |
| Citation | Hemker SL, et al. (2020) Deletion of hypoxia-responsive microRNA-210 results in a sex-specific decrease in nephron number. FASEB J 34(4):5782-5799 |
| abstractText | Low nephron number results in an increased risk of developing hypertension and chronic kidney disease. Intrauterine growth restriction is associated with a nephron deficit in humans, and is commonly caused by placental insufficiency, which results in fetal hypoxia. The underlying mechanisms by which hypoxia impacts kidney development are poorly understood. microRNA-210 is the most consistently induced microRNA in hypoxia and is known to promote cell survival in a hypoxic environment. In this study, the role of microRNA-210 in kidney development was evaluated using a global microRNA-210 knockout mouse. A male-specific 35% nephron deficit in microRNA-210 knockout mice was observed. Wnt/beta-catenin signaling, a pathway crucial for nephron differentiation, was misregulated in male kidneys with increased expression of the canonical Wnt target lymphoid enhancer binding factor 1. This coincided with increased expression of caspase-8-associated protein 2, a known microRNA-210 target and apoptosis signal transducer. Together, these data are consistent with a sex-specific requirement for microRNA-210 in kidney development. |
