Knockdown of miR-26a in zebrafish leads to impairment of the anti-inflammatory function of TnP in the control of neutrophilia


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Article
Language
English
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Open Access
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Abstract
Our recent data show the valuable potential of TnP for the development of a new and safe anti-inflammatory drug due to its ability to control the traffic and activation of leukocytes in response to inflammation. Although there is considerable knowledge surrounding the cellular mechanisms of TnP, less is known about the mechanistic molecular role of TnP underlying its immunomodulatory functions. Here, we conducted investigations to identify whether miRNAs could be one of the molecular bases of the therapeutic effect of TnP. Using a zebrafish model of neutrophilic inflammation with a combination of genetic gain- and loss-of-function approaches, we showed that TnP treatment was followed by up-regulation of only four known miRNAs, and mature dre-miR-26a-1, herein referred just as miR-26a was the first most highly expressed. The knockdown of miR-26a ubiquitously resulted in a significant reduction of miR-26a in embryos, accompanied by impaired TnP immunomodulatory function observed by the loss of the control of the removal of neutrophils in response to inflammation, while the overexpression increased the inhibition of neutrophilic inflammation promoted by TnP. The striking importance of miR-26a was confirmed when rescue strategies were used (morpholino and mimic combination). Our results identified miR-26a as an essential molecular regulator of the therapeutic action of TnP, and suggest that miR-26a or its targets could be used as promising therapeutic candidates for enhancing the resolution of inflammation.
Reference
Falcão MAP, Walker CIB, Disner GR, Silva Filho JB, Soares ABS, Lima LB, et al. Knockdown of miR-26a in zebrafish leads to impairment of the anti-inflammatory function of TnP in the control of neutrophilia. Fish Shellfish Immunol. 2021 July;114:301-310. doi:10.1016/j.fsi.2021.04.029.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/3763
Issue Date
2021


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