Suchergebnisse

Alopecia areata (AA) is a common autoimmune disorder mostly presented as round patches of hair loss and subclassified into alopecia totalis/alopecia universalis (AT/AU) based on the area of alopecia. Although AA is relatively common, only 5% of AA patients progress to AT/AU, which affect the whole scalp and whole body respectively. To determine genetic determinants of this orphan disease, we undertook whole-exome sequencing of 6 samples from AU patients, and 26 variants in immune-related genes were selected as candidates. When an additional 14 AU samples were genotyped for these candidates, 6 of them remained at the level of significance in comparison with 155 Asian controls (p<1.92×10?3). Linkage disequilibrium was observed between some of the most significant SNPs, including rs41559420 of HLA-DRB5 (p<0.001, OR 44.57) and rs28362679 of BTNL2 (p<0.001, OR 30.21). While BTNL2 was reported as a general susceptibility gene of AA previously, HLA-DRB5 has not been implicated in AA. In addition, we found several genetic variants in novel genes (HLA-DMB, TLR1, and PMS2) and discovered an additional locus on HLA-A, a known susceptibility gene of AA. This study provides further evidence for the association of previously reported genes with AA and novel findings such as HLA-DRB5, which might represent a hidden culprit gene for AU. ; This study was partly supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (Green Cosmetic Research Center, A092055) and conducted under a research agreement with AmorePacific Corporation, Republic of Korea. This work was partly supported by the National Research Foundation of Korea [NRF] grant funded by the Korea government [MESF] [No. 2011-0030738]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000045457/1 ; SEQ:1 ; PERF_CD:SNU2013-01 ; EVAL_ITEM_CD:102 ; USER_ID:0000045457 ; ADJUST_YN:N ; EMP_ID:A079130 ; DEPT_CD:801 ; CITE_RATE:4.092 ; FILENAME:lee s, et al plos one 2013.pdf ; DEPT_NM:의학과 ; EMAIL:oskwon@snu.ac.kr ; SCOPUS_YN:N ; CONFIRM:Y

Adipose tissue-derived stem cells (ADSCs) can display multilineage plasticity and share similar characteristics with bone marrow-derived mesenchymal stem cells [1]. Moreover, ADSCs have various cytokine-secreting properties and beneficial paracrine effects on surrounding cells or tissues [2]. Recently, paracrine function is considered one of the most important therapeutic benefits of therapy using mesenchymal stem cells [3,4]. Regarding hair biology, several reports have demonstrated that growth factors from the surroundings stimulate hair growth in ex vivo and animal models [5,6].We have identified secretory factors derived from ADSCs by ELISA and proteomics previously, including IGF binding protein precursors, PDGF, KGF, HGF, VEGF, and fibronectin [7,8]. These factors are well-documented to be related to hair growth stimulation [6]. To determine whether these paracrine effects of ADSCs can promote hair growth, we investigated the effects of ADSCs on hair. ; This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (R01- 2007-000-10491-0). ; Kim WS, 2008, J DERMATOL SCI, V49, P133, DOI 10.1016/j.jdermsci.2007.08.004 ; PARK BS, 2008, DERMATOL SURG ; Cai L, 2007, STEM CELLS, V25, P3234, DOI 10.1634/stemcells.2007-0388 ; Gnecchi M, 2005, NAT MED, V11, P367, DOI 10.1038/nm0405-367 ; Kinnaird T, 2004, CIRC RES, V94, P678, DOI 10.1161/01.RES.0000118601.37875.AC ; Lee RH, 2004, CELL PHYSIOL BIOCHEM, V14, P311, DOI 10.1159/000080341 ; Zuk PA, 2002, MOL BIOL CELL, V13, P4279, DOI 10.1091/mbc.E02-02-0105 ; Elliott K, 1999, J INVEST DERMATOL, V113, P873 ; Danilenko DM, 1996, MOL MED TODAY, V2, P460 ; LIMAT A, 1993, ARCH DERMATOL RES, V285, P205 ; 3