Knockdown of BATF alleviates lung injury in septic neonates through transcriptional regulation of COTL1.

INTRODUCTION

Neonatal sepsis (NS) seriously threatens the health of infants. Coactosin-like protein 1 (COTL1) is a binding protein of F-actin and 5-lipoxygenase which is known to regulate the progression of neonatal sepsis. Nevertheless, the function of COTL1 in NS is not clear.

MATERIAL AND METHODS

An in vivo model of NS was established using cecal slurry (CS). H&E staining was applied for observing the severity of lung injury in tissues of mice. MTT assay was applied for determining cell viability, and the inflammatory factors were examined using ELISA. Apoptosis was assessed via flow cytometry. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) levels were assessed by commercial kits. The interaction between basic leucine zipper ATF-like transcription factor (BATF) and COTL1 was verified using dual luciferase reporter and chromatin immunoprecipitation (ChIP) assay.

RESULTS

COTL1 knockdown alleviated the progression of NS-induced lung injury. COTL1 knockdown enhanced the viability and decreased interleukin (IL)-6 and IL-1 levels in lipopolysaccharides (LPS)-stimulated pulmonary microvascular endothelial cells. Silencing of COTL1 inhibited LPS induced apoptosis and oxidative stress. More importantly, BATF activated MAPK/NF-B signaling through transcriptionally upregulating COTL1. Furthermore, BATF improved the LPS-induced inflammatory response and apoptosis in pulmonary microvascular endothelial cells through mediation of COTL1.

CONCLUSIONS

BATF knockdown alleviated NS-induced lung injury by activating the MAPK/NF-B pathway via transcriptionally upregulating COTL1 expression.