17R-RvD1 protects kidney from sickle cell–related acute injury, prevents inflammatory vascular activation, and positively modulates antifibrotic let7c miRNA. (A) Plasma creatinine (upper panel) and blood urea nitrogen (BUN) (lower panel) levels in AA and SS mice under normoxic conditions or treated with vehicle or 17R-RvD1 (100 ng) and exposed to H/R: hypoxia (8% oxygen; 10 hours), followed by reoxygenation (21% oxygen; 3 hours). Data are mean ± SD (n = 6). *P < .05 vs normoxia, °P < .05 vs healthy mice (AA), ^P < .05 vs vehicle. Hematoxylin and eosin–stained sections of kidney tissue from AA and SS mice treated with vehicle [AA (B); SS (D-E)] or 100 ng of 17R-RvD1 [AA (C); SS (F)] exposed to H/R: hypoxia (8% oxygen; 10 hours) followed by reoxygenation (21% oxygen; 3 hours) (original magnification ×400). Sections of kidney from mice given 17R-RvD1 (C,F) show less glomerular inflammatory cellular infiltrate (in the form of lymphocytes, neutrophils, and plasma cells), glomerular sclerosis (arrow), and thrombi (arrow) compared with vehicle-treated mice (B,D-E); also see Table 1). (G) Immunoblot analysis, using specific antibodies against phosphorylated (P-)NF-κB, NF-κB, P-Nrf2, and Nrf2, in kidney from AA and SS mice treated as in (B). One representative gel from 6 gels with similar results is shown. Densitometric analysis of immunoblots is shown in supplemental Figure 2A. (H) Immunoblot analysis, using specific antibodies against HO-1, IL-6, ET-1, VCAM-1, and TXAS-1, of kidney from AA and SS mice treated as in (B). One representative gel from 6 gels with similar results is shown. Vertical line(s) in ET-1 gel have been inserted to indicate a repositioned gel lane. Densitometric analysis immunoblots are shown in supplemental Figure 2A. (I) Effect of 17R-RvD1 on kidney let7c expression. Levels of miRNA let7c were quantified, using real-time polymerase chain reaction, in kidneys collected from AA and SS mice that were treated as above. Results are mean ± SD from 3 to 6 mice per group.