| First Author | Maruyama K | Year | 2020 |
| Journal | Cell Rep | Volume | 32 |
| Issue | 2 | Pages | 107906 |
| PubMed ID | 32668247 | Mgi Jnum | J:298828 |
| Mgi Id | MGI:6488985 | Doi | 10.1016/j.celrep.2020.107906 |
| Citation | Maruyama K, et al. (2020) Zinc Finger Protein St18 Protects against Septic Death by Inhibiting VEGF-A from Macrophages. Cell Rep 32(2):107906 |
| abstractText | Zinc finger protein St18 was initially reported as candidate tumor suppressor gene, and also suggested that fibroblast St18 positively regulates NF-kappaB activation. Despite the pleiotropic functions of St18, little is known about its roles in macrophages. Here, we report that myeloid St18 is a potent inhibitor of VEGF-A. Mice lacking St18 in myeloid lineages exhibit increased retinal vasculature with enhanced serum VEGF-A concentrations. Despite the normal activation of NF-kappaB target genes, these mice are highly susceptible to LPS-induced shock, polymicrobial sepsis, and experimental colitis, accompanied by enhanced vascular and intestinal leakage. Pharmacological inhibition of VEGF signaling rescued the high mortality rate of myeloid-specific St18-deficient mice in response to inflammation. Mechanistically, St18 directly binds to Sp1 and attenuates its activity, leading to the suppression of Sp1 target gene VEGF-A. Using mouse genetic and pharmacological models, we reveal myeloid St18 as a critical septic death protector. |
