| First Author | Baek JH | Year | 2015 |
| Journal | J Clin Invest | Volume | 125 |
| Issue | 8 | Pages | 3198-214 |
| PubMed ID | 26121749 | Mgi Jnum | J:224537 |
| Mgi Id | MGI:5688231 | Doi | 10.1172/JCI81166 |
| Citation | Baek JH, et al. (2015) IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease. J Clin Invest 125(8):3198-214 |
| abstractText | Macrophages (Mo) are integral in ischemia/reperfusion injury-incited (I/R-incited) acute kidney injury (AKI) that leads to fibrosis and chronic kidney disease (CKD). IL-34 and CSF-1 share a receptor (c-FMS), and both cytokines mediate Mo survival and proliferation but also have distinct features. CSF-1 is central to kidney repair and destruction. We tested the hypothesis that IL-34-dependent, Mo-mediated mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD. In renal I/R, the time-related magnitude of Mo-mediated AKI and subsequent CKD were markedly reduced in IL-34-deficient mice compared with controls. IL-34, c-FMS, and a second IL-34 receptor, protein-tyrosine phosphatase zeta (PTP-zeta) were upregulated in the kidney after I/R. IL-34 was generated by tubular epithelial cells (TECs) and promoted Mo-mediated TEC destruction during AKI that worsened subsequent CKD via 2 distinct mechanisms: enhanced intrarenal Mo proliferation and elevated BM myeloid cell proliferation, which increases circulating monocytes that are drawn into the kidney by chemokines. CSF-1 expression in TECs did not compensate for IL-34 deficiency. In patients, kidney transplants subject to I/R expressed IL-34, c-FMS, and PTP-zeta in TECs during AKI that increased with advancing injury. Moreover, IL-34 expression increased, along with more enduring ischemia in donor kidneys. In conclusion, IL-34-dependent, Mo-mediated, CSF-1 nonredundant mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD. |
