MikroRNAk eta adipokinak: pronostikoko eta erantzun terapeutikoko biomarkatzaileen eta ekintza-mekanismoen bitartekarien bilaketa
61 visitas recibidas
Autoría:
Asier Leniz Rodriguez
Director/a:
Maria Puy Portillo Baquedano, Alfredo Fernandez Quintela
Universidad:
Universidad del País Vasco
Facultad:
Facultad de Farmacia
Departamento:
Farmacia y Ciencias de los Alimentos
Área:
Medicina
Año:
2022
|Doktorego-tesi honen helburua da aztertzea mikroRNAek eta adipozitokinek nola eragiten duten zenbait patologiaren ekintza-mekanismoan, eta horiek nola erabil daitezkeen gaixotasunon garapenaren edo tratamenduekiko erantzunaren biomarkatzaile gisa. Helburu hori lortzeko, hiru ikerketa-proiektu gauzatu ziren. Lehenengoan aztertu zen mikroRNAek eragina izan dezaketela pteroestilbenoak esteatosi hepatikoan dituen efektu positiboetan. Horretarako, zenbait mikroRNAren adierazpena neurtu zen esteatosia duten arratoien gibeleko ehunean, pteroestilbenoarekin tratatu ostean; ondoren, mikroRNA horiek hepatozitoetara transferitu eta zelula-mailan duten ekintza-mekanismoa aztertu zen. Bigarrenean, berriz, aztertu zen mikroRNAek nola eragin dezaketen mahats-patsaren estraktu baten glukosak metabolismoan dituen efektuetan, sindrome metabolikoa duten pertsonengan, eta, bestalde, tratamenduaren erantzun-markatzaile gisa erabil daitezkeen ala ez zehaztu nahi izan zen. Horretarako, hainbat mikroRNAren adierazpena analizatu zen sindrome metabolikoa duten pertsonen odol-laginetan, mahats-patsaren estraktu batekin tratatu aurretik eta ondoren. Horrez gain, tratamenduari erantzun zioten pertsonen eta erantzun ez ziotenen arteko balioak alderatu ziren. Hirugarrenean, adipozitokinek adin gestazionalerako txikiak (TAG) diren haurren hazkuntza-abiaduran parte hartzen ote duten ikertu zen, eta etorkizuneko alterazio metabolikoen markatzailetzat har daitezkeen. Horretarako, zenbait adipokinaren kontzentrazioa analizatu zen bizitzako lehen 2 urteetan hazkuntza-abiadura desberdinak zituzten TAG haurren odolean. Ondorioztatu zenez, mikroRNAek eta adipokinek ekintza-mekanismoetan har dezakete parte, eta hainbat patologiaren erantzun terapeutikoaren eta bilakaeraren markatzaile izan daitezke.This doctoral dissertation aims to analyse the role played by both microRNA and adipocytokines in the action mechanism of various pathologies, plus their potential use as biomarkers regarding development of those diseases or response to their treatment. This was divided into 3 research projects: firstly, analysis on how microRNA might be involved in the positive effects of the pterostilbene on hepatic steatosis. This was done by measuring the expression of a series of microRNA in the hepatic tissue of rats with steatosis treated with pterostilbene and, by transfecting them in hepatocytes, their action mechanism was studied at a cellular level. Secondly, analysis on how microRNA can affect the metabolism of glucose from an extract of grape pomace in persons with metabolic syndrome and, at the same time, determine their possible use as treatment response markers. This was done by analysing the expression of several microRNA in blood samples from people with metabolic syndrome before and after being treated with an extract of grape pomace, also comparing values from subjects who responded to the treatment against those who did not. Thirdly, it was investigated whether adipocytokines could be involved in the growth speed of children who are small for their gestational age (SGA) and possibly be considered markers for future metabolic alterations. This was done by analysing the concentration of several adipokines in the blood of SGA children who demonstrated different growth speeds during the first 2 years of their life. It can be concluded that microRNA and adipokines can intervene in the action mechanisms and be markers for the therapeutic response and evolution of different pathologies.
