| First Author | Khamissi FZ | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 8 | Pages | eabm5900 |
| PubMed ID | 35213222 | Mgi Jnum | J:329156 |
| Mgi Id | MGI:6890031 | Doi | 10.1126/sciadv.abm5900 |
| Citation | Khamissi FZ, et al. (2022) Identification of kidney injury released circulating osteopontin as causal agent of respiratory failure. Sci Adv 8(8):eabm5900 |
| abstractText | Tissue injury can drive secondary organ injury; however, mechanisms and mediators are not well understood. To identify interorgan cross-talk mediators, we used acute kidney injury (AKI)-induced acute lung injury (ALI) as a clinically important example. Using kidney and lung single-cell RNA sequencing after AKI in mice followed by ligand-receptor pairing analysis across organs, kidney ligands to lung receptors, we identify kidney-released circulating osteopontin (OPN) as a novel AKI-ALI mediator. OPN release from kidney tubule cells triggered lung endothelial leakage, inflammation, and respiratory failure. Pharmacological or genetic OPN inhibition prevented AKI-ALI. Transplantation of ischemic wt kidneys caused AKI-ALI, but not of ischemic OPN-global knockout kidneys, identifying kidney-released OPN as necessary interorgan signal to cause AKI-ALI. We show that OPN serum levels are elevated in patients with AKI and correlate with kidney injury. Our results demonstrate feasibility of using ligand-receptor analysis across organs to identify interorgan cross-talk mediators and may have important therapeutic implications in human AKI-ALI and multiorgan failure. |
