interleukin-8 and Polycystic-Kidney-Diseases

The Mxi1 proteins are biochemical and biological antagonists of c-myc oncoprotein. It has been reported that the overexpression pattern of c-myc might be similar to a molecular feature of early and late stages of human autosomal dominant polycystic kidney disease. We identified the cyst phenotype in Mxi1-deficient mice aged 6-12 months using H&E staining. Some chemokines containing a protein domain similar to human IL-8, which is associated with the inflammatory response, were subsequently selected from the up-regulated genes. We confirmed the expression level of these chemokines and measured protein concentrations of IL-8 using ELISA in the Mxi1-knockdown cells. IL-8 was found to be significantly increased in Mxi1-knockdown cells. We found that p38 MAP kinase activation was involved in the signal transduction of the Mxi1-inactivated secretion of IL-8. Therefore, we could suggest that the inactivation of Mxi1 leads to the inflammatory response and has the potential to induce polycystic renal disease.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Blotting, Western; Cell Line; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Flavonoids; Gene Expression; Gene Expression Profiling; Humans; Interleukin-8; Mice; Mice, Knockout; Oligonucleotide Array Sequence Analysis; p38 Mitogen-Activated Protein Kinases; Polycystic Kidney Diseases; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Messenger; Tumor Suppressor Proteins