O papel de RNAs pequenos não codificantes e seu significado após exposição ao veneno de Bothrops jararaca
Data
2021-02-25
Autores
Silva, Andrezza do Nascimento
Orientadores
Sanabani, Sabri Saeed
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A picada venenosa da serpente Bothrops jararaca pode causar dor, edema,
hemorragia, necrose e, em alguns casos, se não tratada, perda de tecido lesado
devido à atividade pró-inflamatória do veneno. Isso se deve à presença de enzimas
ativas e toxinas potentes que compõem o veneno. Um dos componentes principais e
mais abundantes do veneno são as metaloproteases, conhecidas como SVMPs
(snake venom metaloproteinases). A jararagina é uma das SVMPs mais estudadas no
veneno de B. Jararaca e tem a capacidade de promover uma resposta inflamatória
aguda. Pequenos RNAs não codificantes (small non-coding RNAs), como microRNAs
(miRNAs) e RNA de interação com piwi (piRNA), são conhecidos por terem funções
regulatórias em uma variedade de processos celulares, e sua desregulação contribui
significativamente para diversas condições patológicas, incluindo a inflamação.
Atualmente, pouco se conhece sobre a participação de small RNAs na inflamação
local induzida por SVMPs. O objetivo do presente estudo foi determinar se os small
RNAs são regulados na inflamação local desenvolvida em modelo murino, induzida
pela jararagina. Aqui, aplicamos a análise de deep sequencing de small RNA, obtidos
à partir do músculo gastrocnêmio de camundongos incolulados com jararagina em
dois tempos diferentes, com 2h e 24h. O perfil de small RNA dos músculos injetados
com a jararagina (grupo JAR) foi comparado com o musculo gastrocnemio da pata
contralateral injetada com solução salina (grupo PBS). Foram identificados seis e 23
small RNAs expressos diferencialmente (critério de FDR <0,05 e valor de p <0,05,
respectivamente) ao comparar os grupos PBS 24h e JAR 24h e 26 e 65 small RNAs
foram diferencialmente expressos (critério de FDR <0,05 e valor de p <0,05,
respectivamente) ao comparar os grupos JAR 2h e JAR 24h. A expressão diferencial
desses small RNAs participa significativamente de várias vias biológicas, como
resposta inflamatória, senescência celular e tumores como melanoma,
osteossarcoma, carcinoma hepatocelular e tumor neuroendócrino. Esses pequenos
RNAs, recentemente associados à inflamação local induzida pela jararagina, podem
representar marcadores para o risco aumentado de inflamação induzida por
metaloprotease de veneno de serpentes e também podem refletir a diversidade clínica
e patológica em tal inflamação.
The poisonous bite of the Bothrops jararaca snakes can cause pain, edema, hemorrhage, necrosis, and in some cases, if left untreated, can cause loss of injured tissue due to the venom's pro-inflammatory activity. This is due to the presence of active enzymes and potent toxins that are mixed in the jararaca toxin. One of the main and most abundant components of the poison are metalloproteases. Jararhagin is one of the most studied metalloproteases and can promote an acute inflammatory response. Small non-coding RNAs, such as microRNAs (miRNAs) and piwi-interacting RNA (piRNA), are known to have regulatory functions in a variety of cellular processes, and their deregulation significantly contributes to diverse pathological conditions including inflammation. Currently, the specific molecular mechanism of small RNAs in Jararhagin-induced local inflammation has not been determined. The present study aimed to determine whether small RNAs are regulated in Jararhagin-induced local inflammation. Here, we applied deep sequencing analysis to a gastrocnemius muscle of mouse model at 2h and 24h of injection of Jararhagin (JAR group) or saline solution (PBS group) in which small RNA profiling was performed with 20 samples, and six and 23 differentially expressed small RNAs were identified (FDR criterion <0.05 and p - value <0.05, respectively) when comparing PBS 24h and JAR 24h groups; 26 and 65 differentially expressed small RNAs were identified (FDR criterion <0.05 and p-value <0.05, respectively) when comparing JAR 2h and JAR 24h groups. The differential expression of these small RNAs significantly affects various biological pathways such as inflammatory response, cellular senescence and tumors such as melanoma, osteosarcoma, hepatocellular carcinoma, and neuroendocrine tumor. These small RNAs, newly associated with Jararhagin-induced local inflammation, may represent markers for the increased risk of snake venom metalloproteinase-induced inflammation and may also reflect the clinical and pathological diversity in such inflammation.
The poisonous bite of the Bothrops jararaca snakes can cause pain, edema, hemorrhage, necrosis, and in some cases, if left untreated, can cause loss of injured tissue due to the venom's pro-inflammatory activity. This is due to the presence of active enzymes and potent toxins that are mixed in the jararaca toxin. One of the main and most abundant components of the poison are metalloproteases. Jararhagin is one of the most studied metalloproteases and can promote an acute inflammatory response. Small non-coding RNAs, such as microRNAs (miRNAs) and piwi-interacting RNA (piRNA), are known to have regulatory functions in a variety of cellular processes, and their deregulation significantly contributes to diverse pathological conditions including inflammation. Currently, the specific molecular mechanism of small RNAs in Jararhagin-induced local inflammation has not been determined. The present study aimed to determine whether small RNAs are regulated in Jararhagin-induced local inflammation. Here, we applied deep sequencing analysis to a gastrocnemius muscle of mouse model at 2h and 24h of injection of Jararhagin (JAR group) or saline solution (PBS group) in which small RNA profiling was performed with 20 samples, and six and 23 differentially expressed small RNAs were identified (FDR criterion <0.05 and p - value <0.05, respectively) when comparing PBS 24h and JAR 24h groups; 26 and 65 differentially expressed small RNAs were identified (FDR criterion <0.05 and p-value <0.05, respectively) when comparing JAR 2h and JAR 24h groups. The differential expression of these small RNAs significantly affects various biological pathways such as inflammatory response, cellular senescence and tumors such as melanoma, osteosarcoma, hepatocellular carcinoma, and neuroendocrine tumor. These small RNAs, newly associated with Jararhagin-induced local inflammation, may represent markers for the increased risk of snake venom metalloproteinase-induced inflammation and may also reflect the clinical and pathological diversity in such inflammation.