Identification of apolipoproteinA1 reduction in the polycystic kidney by proteomics analysis of the Mxi1-deficient mouse

Abstract

Autosomal dominant polycystic kidney disease is one of the most common human monogenic diseases in which extensive epithelial-lined cysts develop in kidney and other organs. Affected kidneys are not only characterized by the formation of cysts, but also by changes associated with the extracellular matrix and interstitial inflammation, which can progress to fibrosis and loss of renal function. Mxi1 protein, which is a c-myc antagonist, may be essential in controlling cellular growth and differentiation. Previously, multiple tubular cysts were observed in kidney of Mxi1-deficient mice aged 6 months and more. Presently, 2-DE and MALDI-TOF MS was employed to identify the differentially expressed proteins in the kidney. Several proteins were identified, among them, apolipoproteinA1 which is a major component of the high-density lipoprotein complex and has anti-inflammation effects, was significantly decreased in the Mxi1-deficient mouse. We confirm the development of inflammation and renal fibrosis and the expression of extracellular matrix molecules including transforming growth factor were also increased in cystic kidney. These results indicate that expression of proteins related with inflammation and renal fibrosis changes by Mxi1 inactivation in polycystic kidney.