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Methylation of miR‐19b‐3p promoter exacerbates inflammatory responses in sepsis‐induced ALI via targeting KLF7
Author(s) -
Jiang Lingzhi,
Wang Mingshan,
Sun Renhua,
Lin Zongbin,
Liu Renyang,
Cai Hanhui,
Tang Zhiyun,
Zhang Run
Publication year - 2021
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11601
Subject(s) - tumor necrosis factor alpha , proinflammatory cytokine , biology , inflammation , apoptosis , in vivo , flow cytometry , methylation , sepsis , microbiology and biotechnology , cancer research , immunology , gene , biochemistry
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.