Influence on granuloma formation of serine/threonine kinase functioning as a transcription repressor

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860933
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Chiba University
• Principal Investigator: NAKANO Michiyo 千葉大学, 医学部附属病院, 助教 (20645634)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 肉芽腫 / ブラウ症候群 / 若年発症サルコイドーシス / NOD2 / NF-κB / HIPK2

Outline of Final Research Achievements

We performed gene profiling of peripheral CD14+ cells that expressed NOD2 by microarray, and found high expression of serine/threonine kinase HIPK2 (homeodomain-interacting protein kinase 2) in EOS patients. As a result, we studied the relationship of HIPK2 and mutated NOD2 in granuloma formation. We transfected mutants of NOD2 into HEK293 cells and THP1 cells, but there was no difference in HIPK2 mRNA and protein expression between WT and mutants. Therefore, we hypothesized that HIPK2 acts in upstream of NOD2, and its overexpression will up- or down-regulates NOD2. We constructed HIPK2 high expression vector, but we could not transfect the vector into THP1 cells. Therefore, we co-transfected mutants of NOD2 and HIPK2 high expression vector into HEK293 cells, and obtained high expression of NOD2 protein and NF-κB activity, suggesting that HIPK2 upregulates NOD2 and might accelerate granuloma formation.

Free Research Field

皮膚科学