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Targeting the CDA1/CDA1BP1 Axis Retards Renal Fibrosis in Experimental Diabetic
Nephropathy.
Authors Chai Z, Wu T, Dai A, Huynh P, Koentgen F, Krippner G, Ren S, Cooper ME
Submitted By Zhonglin Chai on 12/4/2018
Status Published
Journal Diabetes
Year 2018
Date Published 11/1/2018
Volume : Pages Not Specified : Not Specified
PubMed Reference
Abstract Targeting Cell Division Autoantigen 1 (CDA1) is postulated to attenuate the
profibrotic actions of transforming growth factor-脽 in diabetic nephropathy.
This study has identified a regulatory protein for CDA1 and has then used
genetic and pharmacological approaches to test in vivo if strategies to target
this pathway would lead to reduced renal injury. A novel protein, named CDA1BP1,
was identified as critical in regulating the profibrotic activity of CDA1.
Genetic deletion of CDA1BP1 attenuated key parameters of renal fibrosis in
diabetic mice. Furthermore, a series of short synthetic CDA1BP1 peptides
competitively inhibited CDA1-CDA1BP1 binding in vitro with a hybrid peptide,
CHA-050, containing a 12mer CDA1BP1 peptide and a previously known "Cell
Penetrating Peptide", dose-dependently reducing expression of collagens I and
III in HK-2 cells. In vivo, a D-amino acid retro-inverso peptide, CHA-061,
significantly attenuated diabetes-associated increases in renal expression of
genes involved in fibrotic and pro-inflammatory pathways. In a delayed
intervention study, CHA-061 treatment reversed diabetes associated molecular and
pathological changes within the kidney. Specifically, CHA-061 attenuated
significantly renal extracellular matrix accumulation and glomerular injury.
Taken together, targeting the CDA1/CDA1BP1 axis is a safe, efficacious and
feasible approach to retard experimental diabetic nephropathy.

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