Our recent publication showed that a small bioactive
pigment epithelium derived factor (PEDF)
peptide (P78-PEDF) prevents the development of
diabetic nephropathy (DN). However, its effects on the progression of established DN were not clear. Therefore, the purpose of this study was to determine the effect of P78-PEDF in the progression of DN and to compare the effects of P78-PEDF and an
ACE inhibitor (ACEi), a standard of care in DN. Experiments were conducted in Ins2(Akita) mice treated with P78-PEDF or
captopril starting at 6 wks of age for 12 wks (early treatment) or starting at 12 wks of age for 6 wks (late treatment). We first established the optimal dose of the P78-PEDF
peptide to ameliorate DN in Ins2(Akita) mouse for a 6 wk study period and found that the
peptide was effective at 0.1- 0.5 µg/g/day. We next showed that early or late treatment with P78-PEDF resulted in protection from DN as indicated by reduced
albuminuria, kidney macrophage recruitment, histological changes, inflammatory
cytokines and fibrotic markers (kidney TNF-α,
fibronectin, VEGFA and EGFR), and restored
nephrin expression compared with vehicle-treated Ins2(Akita) mice. Interestingly, only early but not late treatment with
captopril was as effective as P78-PEDF in reducing most DN complications, despite its lack of effect on
nephrin, VEGFA and EGFR expression. These findings highlight the importance of P78-PEDF
peptide as a potential therapeutic modality in both the development and progression of diabetic renal injury.