Inhibition of KLF6 reduces the inflammation and apoptosis of type II alveolar epithelial cells in acute lung injury

Abstract

Background: The development of acute lung injury (ALI) into a severe stage leads to acute respi-ratory distress syndrome (ARDS). The morbidity and mortality of ALI and ARDS are very high. Objective: This study is aimed to explore the effect of Krüppel-like factor 6 (KLF6) on lipopoly-saccharide (LPS)-induced type II alveolar epithelial cells in ALI by interacting with cysteine-rich angiogenic inducer 61 (CYR61). Material and Methods: ALI mice model and LPS-induced type II alveolar epithelial cells were conducted to simulate ALI in vivo and in vitro. The messenger RNA (mRNA) and protein expres-sion of KLF6 in lung tissues were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Pathological changes in lung tissues were observed by hematoxylin and eosin (H&E) staining. The viability and KLF6 expression of A549 cells treated with different concentrations of LPS were detected by cell counting kit-8 (CCK-8) assay, RT-qPCR, and Western blot analysis. After indicated treatment, the viability and apoptosis of A549 cells were analyzed by CCK-8 and TUNEL assays, and the inflammation factors of A549 cells were detected by Enzyme-linked-immunosorbent serologic assay, RT-qPCR, and Western blot analysis. The combination of KLF6 and CYR61 was determined by chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assay. Results: KLF6 expression was increased in lung tissues of ALI mice and LPS-induced A549 cells. Interference with KLF6 improved the viability, reduced the inflammatory damage, and promoted the apoptosis of LPS-induced A549 cells. In addition, KLF6 could bind to CYR61. Interference with KLF6 could decrease CYR61 expression in LPS-induced A549 cells. LPS also enhanced the TLR4/MYD88 signaling pathway, which was reversed by KLF6 interference. The above phenomena in LPS-induced A549 cells transfected with Si-KLF6 could be reversed by overexpression of CYR61. Conclusion: Inhibition of KLF6 promoted the viability and reduced the inflammation and apop-tosis of LPS-induced A549 cells, which was reversed by CYR61.

Silencing KLF6 Alleviates Cigarette Smoke Extract-Induced Mitochondrial Dysfunction in Bronchial Epithelial Cells by SIRT4 Upregulation

“… 8 A previous study has shown that the inhibition of KLF6 can reduce the inflammation and apoptosis of type II alveolar epithelial cells in acute lung injury. 9 Additionally, the trans-activation of iNOS gene by KLF6 can promote apoptosis during respiratory syncytial virus infection. 10 In addition, study has analyzed the differential genes of samples from patients with acute exacerbation of COPD and stable COPD and found that KLF6 is up-regulated.…”

Apigenin-7-glucoside induces apoptosis and ROS accumulation in lung cancer cells, and inhibits PI3K/Akt/mTOR pathway

“…Apoptosis occurs through one of two typical pathways, including death receptor-mediated and mitochondrial pathways [4]. In the mitochondrial pathway, the generated ROS initiates the mitochondrial permeability transition, reducing mitochondrial membrane potential and releasing Cytochrome C [2,5,6].…”