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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2020.tde-19022020-101903
Document
Author
Full name
Lorena Teixeira Frasson
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Santos, Marinilce Fagundes dos (President)
Bonci, Daniela Maria Oliveira
Hamassaki, Dania Emi
Matsuda, Monique
Title in Portuguese
Expressão de Let-7, Lin-28 e HMGA2 nas células progenitoras retinianas do epitélio ciliar de mamíferos.
Keywords in Portuguese
Células-tronco retinianas
Epitélio Ciliar
HMGA
Let-7
Lin-28
Abstract in Portuguese
A retina é um tecido nervoso que pode ser exposto a fatores degenerativos ambientais e genéticos, resultando em perda visual ou cegueira completa. Embora não seja capaz de se regenerar, algumas células epiteliais localizadas na periferia retiniana, na região do Epitélio Ciliar, foram identificadas como células-tronco/progenitoras com capacidade de gerar novos neurônios retinianos. Apesar de possuir capacidade de regeneração do tecido retiniano, esta capacidade não se desenvolve de forma eficiente, indicando a presença de mecanismos inibitórios atuando sobre o potencial regenerativo das células do Epitélio Ciliar (EC). Dentre os mecanismos inibitórios conhecidos atualmente, se encontram os microRNAs. Neste trabalho, demonstramos que os microRNAs da família Let-7 são altamente expressos nas células do EC de mamíferos adultos, principalmente nas células do Epitélio Não-Pigmentado, que não apresentam a capacidade de reprogramação em células-tronco. Estes miRNAs são pouco expressos em animais neonatos e se acumulam nestas células durante o amadurecimento/desenvolvimento do tecido. As proteínas Lin28 e HMGA2, que se apresentam como importantes reguladores de Let-7 e uns dos alvos mais bem descritos na literatura, respectivamente, apresentaram padrão inverso de expressão ao do Let-7, sendo altamente expressas nos animais neonatos, com expressão reduzida ao longo do amadurecimento do tecido. As células do Epitélio Ciliar reprogramadas em células-tronco (neuroesferas) apresentaram a expressão de Let-7 semelhante às de neonatos, com maior expressão de Lin28a e HMGA2. Por fim, a manipulação experimental de Let-7, através de agentes mimetizadores e inibidores desse miRNA, induziu um importante aumento de HMGA2 e uma discreta regulação de Lin-28, sugerindo que o eixo regulatório Lin-28-Let-7-HMGA possa controlar algumas funções nas células do Epitélio Ciliar.
Title in English
Let-7, Lin28 and HMGA2 expression in mammalian retinal progenitor cells.
Keywords in English
Ciliary epithelium
HMGA
Let-7
Lin-28
Retinal stem cells
Abstract in English
The retina is a nerve tissue that can be exposed to environmental and genetic degenerative factors, resulting in visual loss or complete blindness. Although unable to regenerate, some epithelial cells located on the retinal periphery, in the region of the Ciliary Epithelium have been identified as stem / progenitor cells capable of generating new retinal neurons. Despite its ability to regenerate retinal tissue, this capacity does not develop efficiently, indicating the presence of inhibitory mechanisms acting on the regenerative potential of Ciliary Epithelium (CE) cells. Among the currently known inhibitory mechanisms are microRNAs. In this work, we demonstrate that Let-7 family of microRNAs are highly expressed in adult mammalian CE cells, mainly in non-pigmented epithelium cells, which do not have the reprogramming capacity into stem cells. These miRNAs are poorly expressed in newborn animals and accumulate in these cells during tissue maturation / development. The proteins Lin28 and HMGA2, which are important regulators of Let-7 and one of the best described targets in the literature, respectively, showed an inverse expression pattern to Let-7, being highly expressed in newborn animals, with reduced expression with the maturation of the tissue. Ciliary epithelium cells reprogrammed into stem cells (neurospheres) showed similar Let-7 expression to newborns, with higher expression of Lin28a and Hmga2. Finally, the experimental manipulation of Let-7 by mimetic and inhibitors specific agents of this miRNA induced a significant increase of HMGA2 and a slight regulation of Lin-28, suggesting that the regulatory axis Lin-28-Let-7-HMGA may control some of the functions in the cells of the Ciliary Epithelium stem cells.
 
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Release Date
2022-02-18
Publishing Date
2020-02-20
 
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