Inactivation of Mxi1 induces Il-8 secretion activation in polycystic kidney

Kyung Hyun Yoo; Young Hoon Sung; Moon Hee Yang; Jeong Ok Jeon; Yeon Joo Yook; Yu Mi Woo; Han-Woong Lee; Jong Hoon Park

doi:10.1016/j.bbrc.2007.02.103

Inactivation of Mxi1 induces Il-8 secretion activation in polycystic kidney

Biochem Biophys Res Commun. 2007 Apr 27;356(1):85-90. doi: 10.1016/j.bbrc.2007.02.103. Epub 2007 Feb 28.

Authors

Kyung Hyun Yoo¹, Young Hoon Sung, Moon Hee Yang, Jeong Ok Jeon, Yeon Joo Yook, Yu Mi Woo, Han-Woong Lee, Jong Hoon Park

Affiliation

¹ Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.

PMID: 17350592
DOI: 10.1016/j.bbrc.2007.02.103

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Basic Helix-Loop-Helix Transcription Factors
Flavonoids
Interleukin-8
Mxi1 protein, mouse
RNA, Messenger
Tumor Suppressor Proteins
p38 Mitogen-Activated Protein Kinases
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one