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Doctoral Thesis
DOI
10.11606/T.42.2013.tde-29052014-132134
Document
Author
Full name
Alexandre Urban Borbely
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Bevilacqua, Estela Maris Andrade Forell (President)
Francisco, Rossana Pulcineli Vieira
Gama, Patricia
Godosevicius, Sima
Negro, Sonia Jancar
Title in Portuguese
A influência do biglicam mediada por receptores do tipo Toll-like 2 e 4 no processo de invasão das células trofoblásticas.
Keywords in Portuguese
Células trofoblásticas
Gonadotrofina coriônica
Proteoglicanas
Receptores celulares
Trofoblasto
Abstract in Portuguese
O biglicam é um proteoglicano é altamente expresso em células trofoblásticas de patologias placentárias com invasividade exacerbada. No entanto, as funções do biglicam no trofoblasto ainda não foram elucidadas. Sendo assim, verificamos a expressão e as funções de biglicam e seus receptores Toll-like (TLR)-2 e TLR-4 nas células trofoblásticas durante a gestação. As células do citotrofoblasto extraviloso (CTEV) foram positivas para todas as moléculas, menos para o biglicam em placentas a termo. Adição exógena de biglicam promoveu migração e invasão das células trofoblásticas. O biglicam estimulou a fosforilação de AKT nos sítios Thr308 e Ser473 nas células trofoblásticas. A migração e a invasão biglicam-dependentes e as fosforilações de AKT foram inibidas após a adição de anticorpos bloqueadores anti-TLR-2 e anti-TLR-4. O silenciamento gênico de AKT1 em células SGHPL-5 aboliu os efeitos do biglicam na motilidade. Em conclusão, o biglicam aumenta a motilidade de células trofoblásticas após sinalização por AKT através da ativação de TLR-2 e TLR-4.
Title in English
The influence of biglycan mediated by Toll-like receptors 2 and 4 in the invasion of trophoblast cells.
Keywords in English
Cellular receptors
Chorionic gonadotropin
Proteoglycans
Trophoblast
Trophoblast cells
Abstract in English
Biglycan is a highly expressed proteoglycan in trophoblast cells from invasiveness-changed placental pathologies. However, biglycan functions in the trophoblast were not yet identified. Therefore, it was verified the expression and functions of biglycan and its receptors Toll-like (TLR)-2 and TLR-4 in trophoblast cells throughout pregnancy. The extravillous cytotrophoblast cells (EVT) were positive to all the molecules, although biglycan was negative in term placentas. Exogenous biglycan promoted migration and invasion of trophoblast cells. Biglycan stimulated AKT phosphorilation at Thr308 and Ser473 sites in trophoblast cells. The biglycan-dependent migration, invasion and AKT phosphorilation were inhibited upon addiction of anti-TLR-2 and anti-TLR-4 blocking antibodies. AKT1 genic silencing in SGHPL-5 cells abolished the motility effects. In conclusion, biglycan increases the motility of trophoblast cells after AKT signaliing throughout TLR-2 and TLR-4 activation.
 
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Publishing Date
2014-05-30
 
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