2012 Fiscal Year Final Research Report
The mechanisms of transcriptional regulation by microRMAs in relation to COLIA2 promotor region in keloid
| Project/Area Number |
22592003
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Plastic surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
SHIMIZU Hajime 日本医科大学, 老人病研究所, マネージメ ントサポートスタッフ (60398873)
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| Co-Investigator(Kenkyū-buntansha) |
M Ghazizadeh 日本医科大学, 老人病研究所, 准教授 (30190979)
TOSA Mamiko 日本医科大学, 医学部, 講師 (30301568)
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| Project Period (FY) |
2010 – 2012
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| Keywords | ケロイド / microRNA / 線維化 |
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| Research Abstract |
We aimed to investigate expression profiles of microRNAs (miRNAs) in order to understanding the molecular mechanism(s) involved in the pathogenesis of keloid. We confirmed that miR-10a was significantly under-expressed in keloid fibroblasts (KFs) compared with normal dermal fibroblasts (NFs).Inhibition and induction of miR-10a respectively by miRNA inhibitor and retinoic acid (RA) in KFs and NFs revealed that IL-6 and pro-collagen type I (PICP) secretions in the culture supernatants were decreased by miR-10a inhibitor and increased by RA treatment. These results suggest that miR-10a regulates the synthesis and secretion of collagen in KFs and NFs. KF and NF cells were transfected with miR-10a oligonucleotide. The secretion of PICP was reduced in miR-10a transfected KFs and NFs. The miR-10a was significantly over-expressed in KFs and NFs after treatment with RA. The treated cells were harvested for miR-10a qPCR assay and the culture supernatant was analyzed for IL-6 and PICP secretion by ELISA method. The assays indicated that IL-6 concentrations were markedly increased in KFs compared with NFs after RA treatment.Our data confirmed the differential expression of miR-10a in KFs compared with NFs. The miR-10a regulates the synthesis and secretion of collagen in KFs and NFs. Down-regulation of miR-10a may be one of the mechanisms by which collagen is highly deposited in KFs. Our results showed that miR-10a is a promising new effective strategy for targeting keloid lesions.
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