1. LXs reverse established DKD. (A) Study design overview.
LXs reverse established DKD. (A) Study design overview. ApoE−/− mice were rendered diabetic by STZ and diabetes was allowed to progress for 10 weeks, after which a subgroup of diabetic and nondiabetic ApoE−/− mice were administered ethanol (0.1%), LXA4 (5 μg/kg), or Benzo-LXA4 (1.7 μg/kg) twice weekly ip from weeks 10 to 16. (B and C) Paraffin-embedded kidney sections of 16-week intervention study diabetic and control ApoE−/− mice administered ethanol (0.1%), LXA4, or Benzo-LXA4 from weeks 10 to 16 were stained by periodic acid–Schiff stain. Quantification of the glomerulosclerosis injury index is shown in the bar graph as mean±SEM (n=8–10/group; *P<0.05; **P<0.01; ***P<0.001). (D and E) Immunohistochemical staining of collagen IV in glomeruli of paraffin-embedded kidney sections of 16-week intervention study diabetic and control ApoE−/− mice administered ethanol (0.1%), LXA4, or Benzo-LXA4 from weeks 10 to 16. Quantification of staining is shown in the bar graph as mean±SEM (n=8–10/group; *P<0.05). Gene expression analysis of markers of (F) kidney fibrosis and (G) inflammation in kidney cortex tissue isolated from 16-week diabetic and nondiabetic ApoE−/− mice administered vehicle, LXA4, or Benzo-LXA4 from weeks 10 to 16. Expression was normalized to 18S for gene expression analysis (n=8–10, ±SEM; *P≤0.05 versus ApoE−/−+vehicle; φP≤0.05 versus Diabetic ApoE−/−+Vehicle). KO, knockout; qPCR, quantitative polymerase chain reaction.
Eoin P. Brennan et al. JASN 2018;29:
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