Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is an airway‐associated lung disorder, resulting in airway inflammation. This article aimed to explore the role of the krüppel‐like factor 9 (KLF9)/microRNA (miR)‐494‐3p/phosphatase and tensin homolog (PTEN) axis in airway inflammation and pave a theoretical foundation for the treatment of COPD.MethodsThe COPD mouse model was established by exposure to cigarette smoke, followed by measurements of total cells, neutrophils, macrophages, and hematoxylin and eosin staining. The COPD cell model was established on human lung epithelial cells BEAS‐2B using cigarette smoke extract. Cell viability was assessed by cell counting kit‐8 assay. miR‐494‐3p, KLF9, PTEN, and NLR family, pyrin domain containing 3 (NLRP3) levels in tissues and cells were measured by quantitative real‐time polymerase chain reaction or Western blot assay. Inflammatory factors (TNF‐α/IL‐6/IL‐8/IFN‐γ) were measured by enzyme‐linked immunosorbent assay. Interactions among KLF9, miR‐494‐3p, and PTEN 3′UTR were verified by chromatin immunoprecipitation and dual‐luciferase assays.ResultsKLF9 was upregulated in lung tissues of COPD mice. Inhibition of KLF9 alleviated airway inflammation, reduced intrapulmonary inflammatory cell infiltration, and repressed NLRP3 expression. KLF9 bound to the miR‐494‐3p promoter and increased miR‐494‐3p expression, and miR‐494‐3p negatively regulated PTEN expression. miR‐494‐3p overexpression or Nigericin treatment reversed KLF9 knockdown‐driven repression of NLRP3 inflammasome and inflammation.ConclusionKLF9 bound to the miR‐494‐3p promoter and repressed PTEN expression, thereby facilitating NLRP3 inflammasome‐mediated inflammation.

Prdx6 Regulates Nlrp3 Inflammasome Activation-Driven Inflammatory Response in Lens Epithelial Cells

“…It has been reported that dysregulation of antioxidant genes and ROS amplification occur due to suppression of the antioxidant gene by transcription factor Klf9 (Kruppel-like factor) [42][43][44][45], resulting in a sustained increase in ROS production and activation of the Nlrp3 inflammasome pathway. The transcription factor Klf9 (Kruppel-like factor 9) transmodulates genes with a single GC box or repeated GC boxes present in the proximal promoter region of genes [46,47]. Studies have shown the involvement of Klf9 in the regulation of a variety of biological activities, such as cell proliferation, DNA damage, apoptosis and the differentiation of various cell types [45,48,49].…”