RESUMO
Particulate matter (PM) is associated with the incidence, exacerbation, and mortality of variable respiratory diseases. However, the molecular mechanisms of PM10-mediated inflammation are unclear. We identified microRNAs (miRNAs) and messenger RNAs (mRNAs) related to the inflammatory response in PM10-exposed bronchial epithelial cells using next-generation sequencing. Of the miRNAs, miR-6515-5p was significantly downregulated in PM10-exposed human bronchial epithelial BEAS-2B cells. miR-6515-5p regulated the production of pro-inflammatory cytokines (IL-6 and IL-8) and the expression of inflammatory genes (IL-1ß, IL-6, IL-8, TNF-α, CXCL-1, and MCP-1) via MAPK/ERK signaling; overexpression of miR-6515-5p using a mimic inhibited PM10-induced inflammatory responses via inactivation of the ERK pathway, whereas downregulation of miR-6515-5p via an inhibitor significantly increased inflammation in PM10-exposed cells via activation of ERK. Furthermore, we identified colony stimulating factor 3 (CSF3) as a target gene of miR-6515-5p using TargetScanHuman, and confirmed the association between miR-6515-5p and CSF3 using a luciferase reporter assay. Furthermore, we found that mRNA and protein levels of CSF3 were negatively regulated by miR-6515-5p. Inhibition of CSF3 by small interfering RNA significantly reduced the expression and production of inflammatory markers in PM10-exposed cells by inactivating the MAPK/ERK signaling pathway. Therefore, we suggest that miR-6515-5p regulates PM10-induced inflammatory responses by targeting CSF3 via MAPK/ERK signaling in bronchial epithelial cells.
Assuntos
MicroRNAs , Células Epiteliais/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Material Particulado/toxicidadeRESUMO
Astragaloside IV (AS-IV) is one of the major bio-active ingredients of huang qi which is the dried root of Astragalus membranaceus (a traditional Chinese medicinal plant). The pharmacological effects of AS-IV, including anti-oxidative, anti-cancer, and anti-diabetic effects have been actively studied, however, the effects of AS-IV on liver regeneration have not yet been fully described. Thus, the aim of this study was to explore the effects of AS-IV on regenerating liver after 70% partial hepatectomy (PHx) in rats. Differentially expressed mRNAs, proliferative marker and growth factors were analyzed. AS-IV (10 mg/kg) was administrated orally 2 h before surgery. We found 20 core genes showed effects of AS-IV, many of which were involved with functions related to DNA replication during cell division. AS-IV down-regulates MAPK signaling, PI3/Akt signaling, and cell cycle pathway. Hepatocyte growth factor (HGF) and cyclin D1 expression were also decreased by AS-IV administration. Transforming growth factor ß1 (TGFß1, growth regulation signal) was slightly increased. In short, AS-IV down-regulated proliferative signals and genes related to DNA replication. In conclusion, AS-IV showed anti-proliferative activity in regenerating liver tissue after 70% PHx.