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学科主题口腔医学
P-gingivalis Modulates Keratinocytes through FOXO Transcription Factors
Li, Shuai1,2,3; Dong, Guangyu2,3; Moschidis, Anastasios4; Ortiz, Javier4; Benakanakere, Manjunatha R.2,3; Kinane, Denis F.2,3; Graves, Dana T.2,3
刊名PLOS ONE
2013-11-12
DOI10.1371/journal.pone.0078541
8期:11
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]EPITHELIAL-CELLS ; IN-VITRO ; FIBROBLAST APOPTOSIS ; EXPRESSION ; GINGIPAIN ; BACTERIA ; DEGRADATION ; MECHANISM ; INFECTION ; PROTEINS
英文摘要

P. gingivalis is a prominent periodontal pathogen that has potent effects on host cells. In this study we challenged gingival epithelial cells with P. gingivalis with the aim of assessing how mRNA levels of key target genes were modulated by P. gingivalis via the transcription factors FOXO1 and FOXO3. Primary mono- and multi-layer cultures of gingival epithelial cells were challenged and barrier function was examined by fluorescent dextran and apoptosis was measured by cytoplasmic histone associated DNA. Gene expression levels were measured by real-time PCR with and without FOXO1 and FOXO3 siRNA compared to scrambled siRNA. P. gingivalis induced a loss of barrier function and stimulated gingival epithelial cell apoptosis in multilayer cultures that was in part gingipain dependent. P. gingivalis stimulated an increase in FOXO1 and FOXO3 mRNA, enhanced mRNA levels of genes associated with differentiated keratinocyte function (keratin-1, -10, -14, and involucrin), increased mRNA levels of apoptotic genes (BID and TRADD), reduced mRNA levels of genes that regulate inflammation (TLR-2 and -4) and reduced those associated with barrier function (integrin beta-1, -3 and -6). The ability of P. gingivalis to modulate these genes was predominantly FOXO1 and FOXO3 dependent. The results indicate that P. gingivalis has pronounced effects on gingival keratinocytes and modulates mRNA levels of genes that affect host response, differentiation, apoptosis and barrier function. Moreover, this modulation is dependent upon the transcription factors FOXO1 or FOXO3. In addition, a new function for FOXO1 was identified, that of suppressing TLR-2 and TLR-4 and maintaining integrin beta -1, beta -3 and beta -6 basal mRNA levels in keratinocytes.

语种英语
WOS记录号WOS:000327252100029
项目编号DE018307 ; DE019108
资助机构NIDCR
引用统计
被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56104
专题北京大学口腔医学院_口腔种植科
北京大学第三临床医学院_医学工程处
作者单位1.Peking Univ, Dept Implant Dent, Sch & Hosp Stomatol, Beijing 100871, Peoples R China
2.Univ Penn, Sch Dent Med, Dept Pathol, Philadelphia, PA 19104 USA
3.Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA 19104 USA
4.Boston Univ, Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02215 USA
推荐引用方式
GB/T 7714
Li, Shuai,Dong, Guangyu,Moschidis, Anastasios,et al. P-gingivalis Modulates Keratinocytes through FOXO Transcription Factors[J]. PLOS ONE,2013,8(11).
APA Li, Shuai.,Dong, Guangyu.,Moschidis, Anastasios.,Ortiz, Javier.,Benakanakere, Manjunatha R..,...&Graves, Dana T..(2013).P-gingivalis Modulates Keratinocytes through FOXO Transcription Factors.PLOS ONE,8(11).
MLA Li, Shuai,et al."P-gingivalis Modulates Keratinocytes through FOXO Transcription Factors".PLOS ONE 8.11(2013).
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