| First Author | Li ZL | Year | 2019 |
| Journal | Kidney Int | Volume | 95 |
| Issue | 2 | Pages | 388-404 |
| PubMed ID | 30551896 | Mgi Jnum | J:295977 |
| Mgi Id | MGI:6455101 | Doi | 10.1016/j.kint.2018.09.013 |
| Citation | Li ZL, et al. (2019) HIF-1alpha inducing exosomal microRNA-23a expression mediates the cross-talk between tubular epithelial cells and macrophages in tubulointerstitial inflammation. Kidney Int 95(2):388-404 |
| abstractText | Hypoxia promotes tubulointerstitial inflammation in the kidney. Although hypoxia inducible factor-1alpha (HIF-1alpha) is a master regulator of the response to hypoxia, the exact mechanisms through which HIF-1alpha modulates the induction of tubulointerstitial inflammation are still largely unclear. We demonstrated tubulointerstitial inflammation and increased tubular HIF-1alpha expression in murine models of ischemia/reperfusion injury and unilateral ureteral obstruction. Increased expression of HIF-1alpha in tubular epithelial cells was associated with selective shedding of microRNA-23a (miRNA-23a)-enriched exosomes in vivo and systemic inhibition of miRNA-23a prior to ischemia/reperfusion injury attenuated tubulointerstitial inflammation. In vitro, uptake of miRNA-23a-enriched exosomes by macrophages triggered their reprogramming into a pro-inflammatory state via suppression of the ubiquitin editor A20. To confirm the effect of miRNA-23a-containing exosomes on tubulointerstitial inflammation, we exposed tubular epithelial cells to hypoxic conditions to promote the release of miRNA-23a-containing exosomes. Injection of these miRNA-23a-enriched exosomes into uninjured renal parenchyma resulted in increased inflammatory infiltration in vivo. Taken together, our studies demonstrate that the HIF-1alpha-dependent release of miRNA-23a-enriched exosomes from hypoxic tubular epithelial cells activates macrophages to promote tubulointerstitial inflammation. Blockade of exosome-mediated miRNA-23a transfer between tubular epithelial cells and macrophages may serve as a novel therapeutic approach to ameliorate tubulointerstitial inflammation. |
