2005 Fiscal Year Final Research Report Summary
Novel Strategy for Treatment of Keloid ; Application of siRNA and Keratinocyte
| Project/Area Number |
16591792
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Plastic surgery
|
|---|
| Research Institution | HOKKAIDO UNIVERSITY |
|---|
Principal Investigator |
TSUTSUMIDA Arata Hokkaido University, Graduate School of Medicine, Instructor, 大学院・医学研究科, 助手 (00374489)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Yuhei Hokkaido University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (70271674)
SEKIDO Mitsuru Hokkaido University, Hokkaido University Hospital, Lecturer, 講師 (40372255)
OYAMA Akihiko Hokkaido University, Hokkaido University Hospital, Instructor, 助手 (70374486)
FURUKAWA Hiroshi Hokkaido University, Hokkaido University Hospital, Pysician, 医員 (00399924)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | keloid / macrophage migration inhibitory factor (MIF) / lysophosphatidic acid (LPA) / siRNA |
|---|
| Research Abstract |
In 2004, we analyzed the expression of multiple genes of keloid-derived fibroblast, and strong expression of macrophage migration inhibitory factor (MIF) and receptor for lysophosphatidic acid (LPA) has been confirmed. MIF and LPA have been known as key role factors in wound healing and inflammation. However there has not been reported about the relationship between these two molecules in keloid, so we analyzed it. We comfirmed the chemotaxis of fibroblasts derived from keloid was higher than normal skin fibroblasts when they were activated by LPA. And both the molecule and mRNA of MIF were highly induced by LPA stimulation with dose dependent manner. The expression pattern of LPA receptor subtypes was different between keloid-derived fibroblast and normal skin fibroblast. Making them together, we strongly guessed those two molecules, MIF and LPA, were meaningful candidates for novel strategy for treatment of keloid.
In order to achieve our research project of 2005, we decide the use of siRNA of MIF for inhibition of function in keloid-derived fibroblasts. The effect of MIF on chemotaxis of keloid derived fibroblast, and the relation ship between LPA and MIF were also researched. The inhibition of LPA effect (chemotaxis) by siRNA of MlF was confirmed in keloid derived fibroblasts. Rho activation has been also inhibited. In this project, we inhibit MIF function in cytozol of keloid derived fibroblasts using siRNA of MIF, and chemotaxis of them were suppressed. The mechanism included the signaling pathway from LPA activation to Rho.
|
