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miR-145a Regulation of Pericyte Dysfunction in a Murine Model of Sepsis.
Wu, Yan; Li, Pengfei; Goodwin, Andrew J; Cook, James A; Halushka, Perry V; Zingarelli, Basilia; Fan, Hongkuan.
Afiliação
  • Wu Y; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Li P; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Goodwin AJ; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Cook JA; Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Halushka PV; Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Zingarelli B; Department of Pharmacology, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Fan H; Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
J Infect Dis ; 222(6): 1037-1045, 2020 08 17.
Article em En | MEDLINE | ID: mdl-32285112
ABSTRACT

BACKGROUND:

Sepsis is a life-threatening systemic disease with severe microvascular dysfunction. Pericytes preserve vascular homeostasis. To our knowledge, the potential roles of microRNAs in sepsis-induced pericyte dysfunction have not been explored.

METHODS:

We determined lung pericyte expression of miR-145a in cecal ligation and puncture (CLP)-induced sepsis. Mouse lung pericytes were isolated and transfected with a miR-145a mimic, followed by stimulation with lipopolysaccharide (LPS). We measured inflammatory cytokine levels. To assess the functions of miR-145a in vivo, we generated a pericyte-specific miR-145a-knockout mouse and determined sepsis-induced organ injury, lung and renal vascular leakage, and mouse survival rates. We used RNA sequencing and Western blotting to analyze the signaling pathways regulated by miR-145a.

RESULTS:

CLP led to decreased miR-145a expression in lung pericytes. The miR-145a mimic inhibited LPS-induced increases in cytokines. In CLP-induced sepsis, pericytes lacking miR-145a exhibited increased lung and kidney vascular leakage and reduced survival rates. We found that miR-145a could suppress LPS-induced NF-κB activation. In addition, we confirmed that the transcription factor Friend leukemia virus integration 1 (Fli-1) is a target of miR-145a and that Fli-1 activates NF-κB signaling.

CONCLUSION:

Our results demonstrated that pericyte miR-145a mediates sepsis-associated microvascular dysfunction, potentially by means of Fli-1-mediated modulation of NF-κB signaling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sepse / Pericitos / MicroRNAs / Interações Hospedeiro-Patógeno Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sepse / Pericitos / MicroRNAs / Interações Hospedeiro-Patógeno Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article