Veränderung der Nierenfunktion, des Proteoms und des Phosphorylierungsstatus der Proteine bei Alport-Mäusen unter Mycophenolat-Mofetil

Veränderung der Nierenfunktion, des Proteoms und des Phosphorylierungsstatus der Proteine bei Alport-Mäusen unter Mycophenolat-Mofetil

Changes in kidney function, proteom and phoshorylation status of proteins in Alport COL4A3-deficient mice caused by mycophenolat mofetil

Luchs, Klaus

Doctoral thesis

Date of Examination: 2016-11-30

Date of issue: 2016-10-27

Advisor: Oellerich, Michael Prof. Dr. Dr. h.c.

Referee: Gross, Oliver Prof. Dr.

Referee: Schön, Margarete Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-002B-7C50-D

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Abstract

English

Objectives: We aimed to investigate the effects of mycophenolate mofetil (MMF) on kidney function, the proteom and protein phosphorylation in a mouse model for the human Alport syndrome. Methods: COL4A3-deficient (COL4A3-/-) mice were randomly allocated to receive a placebo (PLC COL4A3-/-) or MMF treatment (MMF COL4A3-/-). Wild type mice (WT) were used as controls. Changes in serum creatinine, total protein and blood urea nitrogen (BUN), concentrations of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG), serum protein electrophoresis, urine dipstick chemistry and sediment were measured. Changes in the phosphorylation status of renal proteins, the proteom and histology were analyzed. Results: MMF influenced kidney function, protein phosphorylation. Serum creatinine and BUN were lower in MMF-treated compared to PLC treated COL4A3-/- mice. Serum albumin and alpha-1 globulins were significantly decreased while serum creatinine, alpha-2 globulins, urine dipstick protein, leukocyte esterase, hemoglobin and red blood cells were all increased in both COL4A3-/- groups compared to WT. Differential 2DE-gel-analysis identified six phosphorylated kidney protein spots and four silver stained protein spots that were significantly altered by MMF. Conclusion: These data suggest that the MMF treatment in this murine model moderately improved kidney function, reversed the phosphorylation status of six renal phosphoproteins and the amount of four proteins to that seen in WT mice.

Keywords: mycophenolic acid; kidney fibrosis; phosphorylation; Alport syndrome; proteom