Methylation of miR-19b-3p promoter exacerbates inflammatory responses in sepsis-induced ALI via targeting KLF7.

Sepsis-induced acute lung injury is associated with dysregulated inflammatory reactions. MiR-19b-3p level was reported to be downregulated in patients with sepsis. To evaluate the role of miR-19b-3p in sepsis, cecum ligation and puncture-induced mouse sepsis model and lpopolysaccharide (LPS)-treated pulmonary microvascular endothelial cells (PMVECs) were used. For in vivo study, lung tissue was harvested for hematoxylin and eosin (H&E) staining, tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β, and p-p65, p-IκB measuring. Cell apoptosis was assessed by TUNEL assay. For in vitro study, cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. Methylation of miR-19b-3p promoter was measured by methylation-specific PCR (MSP) assay. The target of miR-19b-3p was determined by dual-luciferase reporter gene assay. The level of miR-19b-3p was determined to be downregulated in vitro and in vivo. In addition, miR-19b-3p protected mice from inflammation injury through inhibiting NF-κB signaling pathway. Overexpression of miR-19b-3p increased cell viability, decreased apoptosis, and proinflammatory cytokines secretion in LPS-treated PMVECs. Besides these, Krüppel-like factor 7 (KLF7) was confirmed as the target of miR-19b-3p. And methylation of miR-19b-3p was the reason of decreased miR-19b-3p level. In conclusion, miR-19b-3p protected cells from sepsis-induced inflammation injury via inhibiting NF-κB signaling pathway, and KLF7 was a potential target. © 2021 International Federation for Cell Biology.

Citation

Lingzhi Jiang, Mingshan Wang, Renhua Sun, Zongbin Lin, Renyang Liu, Hanhui Cai, Zhiyun Tang, Run Zhang. Methylation of miR-19b-3p promoter exacerbates inflammatory responses in sepsis-induced ALI via targeting KLF7. Cell biology international. 2021 Aug;45(8):1666-1675

Mesh Tags

Substances

PMID: 33760339

search → result