Stress signaler p38 mitogen-activated kinase activation: a cause for concern?
Clin Sci (Lond)
; 136(22): 1591-1614, 2022 11 30.
Article
em En
| MEDLINE
| ID: mdl-36250628
ABSTRACT
Oxidative stress (OS) induced activation of p38 mitogen-activated kinase (MAPK) and cell fate from p38 signaling was tested using the human fetal membrane's amnion epithelial cells (AEC). We created p38 KO AEC using the CRISPR/Cas9 approach and tested cell fate in response to OS on an AEC-free fetal membrane extracellular matrix (ECM). Screening using image CyTOF indicated OS causing epithelial-mesenchymal transition (EMT). Further testing revealed p38 deficiency prevented AEC senescence, EMT, cell migration, and inflammation. To functionally validate in vitro findings, fetal membrane-specific conditional KO (cKO) mice were developed by injecting Cre-recombinase encoded exosomes intra-amniotically into p38αloxP/loxP mice. Amnion membranes from p38 cKO mice had reduced senescence, EMT, and increased anti-inflammatory IL-10 compared with WT animals. Our study suggested that overwhelming activation of p38 in response to OS inducing risk exposures can have an adverse impact on cells, cause cell invasion, inflammation, and ECM degradation detrimental to tissue homeostasis.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases p38 Ativadas por Mitógeno
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Mitógenos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article