title: Delayed Treatment with a Small Pigment Epithelium Derived Factor (PEDF) Peptide Prevents the Progression of Diabetic Renal Injury.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Nephrology, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Alaa S
authors.initials: AS
authors.lastname: Awad
authors.affiliation: Department of Medicine, Division of Nephrology, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Hanning
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Medicine, Division of Nephrology, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Ting
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Anzor
authors.initials: A
authors.lastname: Gvritishvili
authors.affiliation: Department of Comparative Medicine, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Cooper
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America; Department of Ophthalmology, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Joyce
authors.initials: J
authors.lastname: Tombran-Tink
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005136:Eye Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D015843:Serpins / Q000494:pharmacology / Q000627:therapeutic use*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D002216:Captopril; D016207:Cytokines; D005136:Eye Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C113267:nephrin