title: Inactivation of Mxi1 induces Il-8 secretion activation in polycystic kidney.
abstract: 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.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Yoo
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Sung
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Yang
authors.forename: Jeong Ok
authors.initials: JO
authors.lastname: Jeon
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Yook
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Woo
authors.forename: Han-Woong
authors.initials: HW
authors.lastname: Lee
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005419:Flavonoids; D016209:Interleukin-8; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C512788:Mxi1 protein, mouse; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one